Journal articles on the topic 'Psoriasis, T helper 17 cells, biologic therapy'
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Kandalova, Olga В., Dina E. Klyuchnikova, and Tatyana V. Ayvazova. "Pathogenesis of psoriasis: past, present, future." Russian Journal of Skin and Venereal Diseases 25, no. 3 (October 13, 2022): 191–200. http://dx.doi.org/10.17816/dv108870.
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Psoriasis is a common, chronic, systemic immune-mediated inflammatory disease that affects the skin, joints, and other organs and systems. Despite the fact that psoriasis is one of the most studied dermatoses, its pathogenesis has not yet been fully clarified. In recent years, the pathogenetic model leading to the formation of psoriatic papules and plaques has undergone significant changes.
This article presents a retrospective analysis of the study of the disease over the past 60 years from the generally accepted concept of epidermal dermatosis to understanding the complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells, with a significant role of interleukins (IL) 23, 17, 22,10, T-helper cells (Th) 17, 22, T-regulatory cells, transformative growth factor b1 (TGF-b1), in the pathogenesis of the disease. Targeted therapy using new biologics and small molecules, patient education, screening for comorbidities, and regular patient follow-up allow to apply a personalized approach to the patient and achieve impressive results.
Achievements in psoriasis research have led to the fact that today we are witnessing the so-called translational revolution in psoriasis therapy, consisting in the fastest possible transfer of fundamental discoveries of the field of theoretical research to the field of practical application.
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Satoh, Y., K. Nakano, H. Yoshinari, S. Nakayamada, S. Iwata, S. Kubo, I. Miyagawa, et al. "A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab." Lupus 27, no. 7 (March 9, 2018): 1202–6. http://dx.doi.org/10.1177/0961203318762598.
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It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.
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Zhukova, O. V., E. I. Kasikhina, M. N. Ostretsova, and N. N. Potekaev. "New possibilities of systemic therapy of plaque psoriasis with the IL23p19 inhibitor risankizumab." Meditsinskiy sovet = Medical Council, no. 8 (June 7, 2021): 40–50. http://dx.doi.org/10.21518/2079-701x-2021-8-40-50.
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Introduction. There is a trend towards rising incidence of psoriasis and increase in the degree of incidence of severe, atypical and treatment-resistant clinical forms of psoriasis in the Russian Federation. In this regard, cases of early disability of patients and deterioration of their quality of life are recorded, which determines the medical and social significance of this disease. In the last few years, a much deeper understanding of the pathogenesis of psoriasis has been gained. This is especially true of the role of T-helper 17 cells, the role of the IL-23 cytokine in the development of the disease, which has resulted in the development of new classes of biological drugs, which creation introduced significant changes in the treatment of psoriasis that has become more effective, safer and convenient for patients. More new biologics undergo clinical trials and receive approvals with each passing year. Among them is risankizumab, interleukin-23 inhibitor, which is a safe and effective drug for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adult patients. Interleukin-23 inhibitors are not required to be administered as often as interleukin-17 inhibitors and may have a more favourable safety profile without an increased risk of candidiasis or inflammatory bowel disease. Overall, these highly effective drugs contribute to the improvement of the long-term efficacy of psoriasis therapy due to relief of skin lesions and joint symptoms, as well as to the enhancement of patients’ quality of life and lengthening of remissions.Purpose. To analyse key information about risankizumab using the results of clinical trials published in the current scientific literature.Materials and methods. This analysis used literature sources from the international medical databases: PubMed, Cochrane Library, MEDLINE.Results. Presently, a number of phase III registrational trials of risankizumab in 2,109 patients with plaque psoriasis have been published: UltIMMa-1, UltIMMa-2, IMMvent and IMMhance, as well as an additional side by side comparative study of risankizumab with secukinumab (IMMerge) in 327 patients with plaque psoriasis. The results of these studies were used as the grounds for approval of risankizumab for the treatment of patients with moderate to severe plaque psoriasis and psoriatic arthritis by the Russian Ministry of Health on September 14, 2020. There have also been several reports of interim results of the open-label enhanced LIMMitless study, which included patients from pivotal studies. Our records show that the percentage of patients receiving risankizumab for 3 years (172 weeks) and maintaining PASI 90 and PASI 100 was 88 and 63%, respectively, and the percentage of those maintaining sPGA 0/1 was 88%.Conclusion. The analysed data showed that risankizumab is one of the most effective target drugs for the treatment of psoriasis and psoriatic arthritis, it has a favourable safety profile and a more convenient dosage regimen as compared with other genetically engineered biologic drugs (GEBD) (the recommended dose of Skyrizi is 150 mg (two 75 mg injections) administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter).
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Flores, Rodrigo, Raúl de la Fuente, Francisca Bozán, Karen Vergara, and Fernando Valenzuela. "Actualización en terapia biológica para psoriasis y artritis psoriática (parte I): moléculas pequeñas, inhibidores de JAK y agentes biológicos (inhibidores IL-17)." Latin american journal of clinical sciences and medical technology 2, no. 2 (July 15, 2020): 113–25. http://dx.doi.org/10.34141/ljcs6065977.
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Psoriasis is a chronic, inflammatory skin disease associated with cardiovascular comorbidities, metabolic syndrome, neoplasms, psychiatric impairment, and arthritis, among others, which affect patients’ quality of life, as well as their life expectancy. Even though it is a multifactorial process of unknown causes, its relationship to class 1 HLA alleles and their polymorphisms has been described. Its physiopathology involves a dysregulation of the systemic inflammatory response —mediated by T Helper lymphocytes, dermal cells, cytokines, and interleukins—, as well as their interactions with keratinocytes and synovial cells. This triggers differentiation of lymphocytes towards a Th 17 phenotype, which activates inflammatory processes mediated mainly by interleukin 17 (IL-17), with the subsequent proliferation of keratinocytes and inflammatory and angiogenic mediators, resulting in the typical cutaneous and osteoarticular clinical features. Biological agents are recombinant proteins produced in different cell lines aimed at interrupting inflammatory pathways in psoriasis and psoriatic arthritis, specifically, immune or genetic mediators involved in the progression of these diseases, ultimately targeting the IL-23 / IL-17 axis. This review aims to discuss the most recent literature regarding the use of small molecules, JAK inhibitors, and biological agents (IL-17 inhibitors) in the treatment of psoriasis and psoriatic arthritis, mainly referring to their efficacy and safety. Using these molecules means a fundamental change in the approach to patients with psoriasis and psoriatic arthritis. As a specific mediator-targeted therapy, it enhances effectiveness, and at the same time, reduces the associated adverse effects. Therefore, it is essential to know how they work from a physiopathological point of view, as well as assessing their effectiveness in humans through randomized clinical trials. Current knowledge allows us to conclude that despite biological agents being the best treatment option in psoriasis as well as in psoriatic arthritis, comparative studies —among drugs of the same group and groups— are still required. Besides, their high price is another problem to solve before they can be massively used in these patients.
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Roy, Amit Kumar, Fahad Al Basir, Priti Kumar Roy, and Amar Nath Chatterjee. "A model analysis to measure the adherence of Etanercept and Fezakinumab therapy for the treatment of psoriasis." Nonlinear Analysis: Modelling and Control 27 (March 16, 2022): 1–21. http://dx.doi.org/10.15388/namc.2022.27.26483.
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This article deals with a immunological model, which includes multiple classes of T cells, namely, the naive T cell, type I, type II and type 17 T helper cells (Th1, Th2, Th17), regulatory T cell (Treg) along with the activated natural killer cells (NK cells) and epidermal keratinocytes. In order to describe the etiology of psoriasis development, we have studied the basic mathematical properties of the model, existence and stability of the interior equilibrium. We have also derived the drug-induced mathematical model using impulse differential equation to determine the effects of combined biologics Etanercept (TNF-α inhibitor) and Fezakinumab (IL-22 monoclonal antibody) therapy considering perfect dosing during the inductive phase. We have determined the required dosing interval of both drugs to maintain the keratinocytes concentration below a threshold level. This study shows that Etanercept alone could theoretically maintain the keratinocytes level, whereas frequent dosing of Fezakinumab alone may not be enough to control the hyper-proliferation of keratinocytes. Furthermore, combination of the drugs with perfect dosing has the noticeable effect on keratinocytes dynamics, which may be suitable therapeutic approaches for treatment of psoriasis.
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Baker, Kenneth F., and John D. Isaacs. "Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?" Annals of the Rheumatic Diseases 77, no. 2 (August 1, 2017): 175–87. http://dx.doi.org/10.1136/annrheumdis-2017-211555.
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The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.
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Christoforou, T., G. Almanzar, F. Brauneiser, N. Buschmann, M. Feuchtenberger, M. Schmalzing, H. P. Tony, M. Goebeler, and M. Prelog. "AB0040 IMPAIRED REGULATORY T CELL FUNCTIONS IN PATIENTS WITH PSORIASIS ARTHRITIS ELIGIBLE TO SWITCH TO ANTI-IL-17 TREATMENT." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1322.2–1323. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6389.
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Background:A dysbalance between Th17 and regulatory T cells (Treg) has been suggested for several T cell-mediated autoimmune disorders. Inhibitors of IL-17 are successfully used for treatment of psoriasis arthritis (PsA). However, so far reconstitution of Treg functions has not been studied in detail in PsA eligible for switching to anti-IL-17 treatment.Objectives:The project aims to analyze the reconstitution and maintenance of regulatory T cell (Treg) function after inhibition of inflammatory Th17-inducing pathways mediated by IL-1, IL-6, IL-17 and TNFalpha in a longitudinal manner.Methods:Therefore, Treg derived from 12 PsA patients switching to Th17 inhibition and healthy controls were phenotypically characterized by flow cytometry. Function was investigated by analysis of suppressive activity of Treg on proliferation of autologous effector T cells in vitro utilizing suppression assays.Results:First results at the time-point of switching to anti-IL-17 treatment demonstrated PsA to be an IL-17-driven T cell-mediated autoimmune disorder, as proportions of T cells with Th17 phenotype were increased in PsA compared to controls (CCR6+IL-17 + 4.9% vs. 0.8% of CD4+) and FoxP3+ Treg cells (CD25brightFoxP3 + 0.2% vs. 0.4% of CD4+) were decreased. Higher proportions of FoxP3+ T cells expressing the Th17-characteristic chemokine receptor CCR6 were found in PsA (4.8% vs. 2.7% of CD4+), as well as higher proportions of pro-apoptotic CD95-expressing FoxP3+ T cells (9.8% vs. 2.8% of CD4+). Less suppression of autologous effector T cells co-cultured with CD25+ Treg cells was found in PsA compared to controls (22.2% vs. 28.3% reduction of proliferative activity), whereas CD25- helper T cells did not contribute to the suppression of effectors in PsA and only minimally in controls. Intracellular IL-10 production in Tregs, a key cytokine of Treg-associated regulation of inflammation, was similar between PsA and controls, although a trend to lower CTLA-4 expression involved in inhibition of co-stimulation was found in PsA.Conclusion:The current results indicate a skewed T cell balance towards Th17 cells and Treg cells showing Th17-like features in samples of PsA unsuccessfully pre-treated with different biologics recommending them for a switch to a therapy with selective inhibition of IL-17. Longitudinal results regarding the reconstitution and maintenance of Treg function in those PsA patients have to be awaited.Disclosure of Interests:Timotheos Christoforou: None declared, Giovanni Almanzar Grant/research support from: Pfizer, Franziska Brauneiser: None declared, Nils Buschmann: None declared, Martin Feuchtenberger Consultant of: Abbvie, BMS, Chugai, Sanofi, Speakers bureau: Abbvie, BMS, Celgene, Chugai, Jansen-Cilag, Lilly, Pfizer, Roche, Sanofi, UCB, Marc Schmalzing Consultant of: Paid consultant for Hexal AG, Hans-Peter Tony Consultant of: AbbVie, Astra-Zeneca, BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Matthias Goebeler: None declared, Martina Prelog Grant/research support from: Chugai, Sobi, Novartis, Pfizer, Baxter, Consultant of: GSK, Pfizer, Novartis, MSD, Baxter, Sobi, Johnson, Speakers bureau: GSK, Pfizer, Novartis, MSD, Baxter, Sobi, Johnson
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Ahmed Shaheen, Aciel, Ismail Hader, and Zakaria Aqel. "Novel Presentation of Terminal Ileitis Associated with Secukinumab Therapy." Case Reports in Gastrointestinal Medicine 2021 (September 28, 2021): 1–4. http://dx.doi.org/10.1155/2021/5213876.
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Inflammatory bowel disease (IBD) and psoriasis are chronic inflammatory immune-mediated diseases. The interleukin-23- (IL23-) T helper (Th)17 pathway has been implicated in their pathogenesis, with multiple biologic therapies targeting this pathway. IL-17, the main proinflammatory cytokine produced by (TH)17, has been targeted by antibodies and IL-17 receptor blockers with favorable outcomes in treating psoriasis and psoriatic arthritis. However, their role in IBD is unpredictable as studies reported worsening of IBD with agents targeting IL-17 and rare case reports with new-onset IBD. We present a case of Crohn's-like severe terminal ileitis and worsening diverticulitis complicated by intestinal perforation requiring total parenteral nutrition shortly after being started on secukinumab.
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Vojdani, Aristo, and Jama Lambert. "The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part I." Evidence-Based Complementary and Alternative Medicine 2011 (2011): 1–8. http://dx.doi.org/10.1093/ecam/nep062.
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CD4+effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-β, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-βand IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.
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Pithadia, Deeti J., Kelly A. Reynolds, Erica B. Lee, Wilson Liao, and Jashin J. Wu. "Tildrakizumab in the treatment of psoriasis: latest evidence and place in therapy." Therapeutic Advances in Chronic Disease 10 (January 2019): 204062231986565. http://dx.doi.org/10.1177/2040622319865658.
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Psoriasis is a chronic inflammatory disorder that is clinically characterized by scaly cutaneous plaques. New evidence suggests that dysregulation of interleukin (IL)-23, a key cytokine in the T-helper-17 pathway, plays a vital role in the development of psoriatic systemic inflammation. The novel biologic medication tildrakizumab is among the first drugs with specific action against IL-23 that has recently been approved by the United States Food and Drug Administration and the European Medicines Agency for moderate-to-severe psoriasis. Tildrakizumab has been shown in large randomized controlled trials to be effective in improving skin manifestations as well as enhancing quality of life outcomes in patients with psoriasis. Its simple dosing, prolonged duration of action, and mild adverse event profile make it a practical option for patients; however, only a small number of trials have investigated the clinical effectiveness of tildrakizumab, and long-term data regarding the drug’s efficacy and safety are currently limited. Hence, further research is needed to better understand the risks and benefits of tildrakizumab. This review summarizes and analyzes phase I, phase II, and phase III clinical trials that investigate the mechanism, pharmacokinetics, efficacy, and safety of tildrakizumab. It also identifies areas in which additional studies are warranted to further elucidate the advantages of tildrakizumab over other biologic therapies.
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Katz, Kimberly L., Katherine Rupley, Jacquelyn Sink, Adele Shuley, and Alice B. Gottlieb. "Interleukin-17 Inhibition in a Patient With Psoriasis and Concurrent Vitiligo." Journal of Psoriasis and Psoriatic Arthritis 3, no. 4 (October 2018): 126–30. http://dx.doi.org/10.1177/2475530318788943.
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Background: Psoriasis and vitiligo are 2 autoimmune conditions that can occur concurrently in patients. At present, no single systemic therapy has been identified to be effective in treating both the conditions. Observations: Recent advances in our understanding of the T helper (Th) 17 subset of Th cells suggests that interleukin (IL)-17 may play a key role in the pathogenesis of both vitiligo and psoriasis. We report a case of anatomically superimposed psoriatic plaques and vitiligo for which treatment with ixekizumab leads to resolution of psoriasis but did not improve the patient’s vitiligo. Conclusion: While IL-17 is highly effective in the treatment of psoriasis, it does not seem to be an effective treatment for vitiligo.
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Petrichuk, S. V., T. V. Radygina, D. G. Kuptsova, O. V. Kurbatova, E. L. Semikina, N. N. Murashkin, A. S. Potapov, and A. P. Fisenko. "Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations." Russian Journal of Immunology 25, no. 4 (October 7, 2022): 491–98. http://dx.doi.org/10.46235/1028-7221-1191-eoa.
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Nuclear transcription factor B (NF-B) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-B signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices ( 10, remission). The number of cells with NF-B translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-B translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-B in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-B activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-B activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-B activity was elevated only in T-helper cells. The level of NF-B translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from exacerbation/remission states assessed as the NK cell numbers with NF-B translocation showed a good quality of the stratification model (AUC 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-B translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-B activation in lymphocyte populations in the children with IBD and psoriasis.
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Wang, Honglin, Sha Yan, Lingyun Zhang, Fang Ke, Jing Bai, Zhaoyuan Liu, Zhenyao Xu, and Jinliu Liu. "Interleukin-17 Targets Ppp6c for epidermal hyperplasia via NF-kappaB-dependent MicroRNA miR-31 induction (HUM7P.300)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 184.9. http://dx.doi.org/10.4049/jimmunol.192.supp.184.9.
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Abstract The efficacy of monoclonal antibodies against either interleukin (IL)-17 or the IL-17 receptor in psoriasis therapy provides strong evidence that IL-17 is the major inflammatory mediator in this disease. However, it is unclear how IL-17 induces epidermal basal keratinocyte hyperproliferation in psoriasis. To explore the mechanism of IL-17 in epidermal hyperplasia in psoriasis, we focused on microRNA(s) induced by IL-17 as these small non-coding RNAs play an important role in regulation of cellular proliferation. Among all the microRNAs we screened, microRNA-31 (miR-31) is the only one extremely sensitive towards IL-17 for its induction in keratinocytes. Its expression in both the epidermis of lesional skin of human psoriasis patients and mouse psoriasis models is IL-17 inducible and NF-kappaB dependent. A causal relationship between IL-17-dependent miR-31 induction and basal keratinocyte hyperproliferation has been then established by constructing and analyzing epidermal conditional knockout of miR-31 (miR-31fl/fl/Keratin 5-Cre) engineering animals. A careful genomic analysis led us to realize that miR-31 targets protein phosphatase 6 (ppp6c), a negative regulator restricting G1 to S phase progression. As expected, ppp6c is suppressed by IL-17 through the miR-31 induction and is diminished in human psoriatic epidermis. We thus have uncovered a novel mechanism that helps explain how T helper (Th)-17 cells signal to basal keratinocytes for their hyperproliferation in psoriasis.
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Whitley, Sarah K., Mushi Li, Tracy Tabib, Casey T. Weaver, Mandy J. McGeachy, Robert A. Lafyatis, and Daniel H. Kaplan. "IL-23 maintains tissue resident memory Th17 cells in murine and psoriatic skin." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 98.50. http://dx.doi.org/10.4049/jimmunol.206.supp.98.50.
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Abstract Tissue resident memory Th17 cells (TRM17) are the key cell type driving the chronic skin inflammation of psoriasis. Although IL-23 is strongly associated with autoimmunity and chronic inflammatory disorders including psoriasis, and anti-IL-23 biologic agents have remarkable efficacy in the treatment of psoriasis, the precise role of IL-23 in supporting IL-17-mediated skin inflammation remains unclear. In mice, we found that circulating memory T cells were dispensable for anamnestic protection from C. albicans skin infection, and TRM17 mediated protection from C. albicans reinfection required IL-23. Administration of anti-IL-23R antibody to dual Il17aCre Rosa26CAG-fl/fl-tdTomato Il17fThy1.1/Thy1.1 (17Fate) fate reporter mice following resolution of primary C. albicans infection resulted in a selective reduction in the number of CD69+CD103+TRM17 cells in skin compared with isotype controls. TRM17 proliferation was reduced and survival was unaffected. CD301b+ dermal dendritic cells (dDC) were an obligate source of IL-23 that supported TRM17 maintenance in skin after C. albicans challenge. These data demonstrate that locally produced IL-23 promotes in situ TRM17 proliferation to support their long term retention in skin. In normal human skin, we identified dermal cDC2 as the principal source of IL-23, although keratinocytes and CD4+ T cells were additional sources of IL-23 in psoriasis skin. Analysis of human psoriasis skin before and after clinical anti-IL-23 therapy revealed reduced TRM17 number and proliferation index, suggesting that targeted depletion of pathogenic TRM17 is the major mechanism by which anti-IL-23 therapy induces uniquely durable disease-free intervals in psoriasis patients.
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Zhu, Shu, and Youcun Qian. "IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential." Clinical Science 122, no. 11 (February 10, 2012): 487–511. http://dx.doi.org/10.1042/cs20110496.
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IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases.
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Mitra, Debdeep. "811. A Randomized Controlled Trial of Prednisolone vs. Interleukin 17 A Inhibitor Secuinumab in the Management of Type 1 Lepra Reaction in Leprosy Patients." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S290. http://dx.doi.org/10.1093/ofid/ofy210.818.
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Abstract Background Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae. Type 1 lepra reactions (T1R) are delayed hypersensitivity (Type IV) reactions which if not treated promptly leads to disability affecting eyes, hands and feet. IL-17 A which is produced mainly by inflammatory T helper 17 cells is up regulated in patients of Lepra reaction. Conventionally oral corticosteroids steroids have been the main stay in the management of Type 1 lepra reactions. This novel biologic drug is a targeted therapy which blocks the offending interleukin molecule without any serious adverse effects. We report the results of this randomized control study wherein an immuno-modulator biologic molecule has been safely used to treat an inflammatory reaction in a chronic infectious disease. Outcomes were measured using recurrence rate, a clinical severity score, quality of life, and adverse events. Methods Seventy-four patients with new T1R were randomized to receive Secukinumab (a human IgG1κ monoclonal antibody that binds to the protein interleukin (IL)-17A) or Prednisolone for 20 weeks. IL-17 A levels were correlated before and after the intervention. Results Recovery rates in skin signs was similar in both groups (92% vs. 87%). Improvements in nerve function both, new and old, sensory (67% vs. 48%) and motor (73% vs. 76%) loss were higher (but not significantly so) in the patients on Secukinumab. Recurrences rates of lepra reaction (25%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients on Secukinumab, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were much lesser with Secukinumab as compared with Prednisolone alone. Both groups had a significant improvement in their quality of life after the study, measured by the Short form survey SF-36. Conclusion This is the first double-blind randomized control trial assessing Secukinumab, in the management of lepra reaction. It could be a safe alternative second-line drug for patients with leprosy reactions who are not improving with prednisolone or are experiencing adverse events related to prednisolone. IL-17A levels could be an important diagnostic marker to diagnose and prognosticate cases of Type 1 Lepra reaction, which if not treated in time can lead to irreversible nerve damage. Disclosures All authors: No reported disclosures.
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Kolar, M., M. Lukas, K. Malickova, L. Prochazkova, M. Bortlik, D. Duricova, V. Hruba, et al. "P368 Tofacitinib induction efficiency and intracellular cytokine dynamics in ulcerative colitis: Results from clinical practice." Journal of Crohn's and Colitis 14, Supplement_1 (January 2020): S348. http://dx.doi.org/10.1093/ecco-jcc/jjz203.497.
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Abstract Background Tofacitinib is an oral JAK inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials; however, data from clinical practice are insufficient. Our aim was to evaluate response to tofacitinib after 8 weeks in UC patients, and to assess potential predictors of response including early cytokine production shifts. Methods Data from consecutive UC patients who started tofacitinib 10 mg b.i.d. were evaluated. Disease activity was assessed by Mayo score at baseline and week 8 together with C-reactive protein (CRP) and faecal calprotectin (FC). Production of IL-4, IL-10, IL-17, TNFα and IFNγ in T-helper cells was determined at baseline and week 4. At week 8, patients with total Mayo 0–5 with endoscopic subscores 0–1 were considered responders. Adverse events were registered at every visit. Results Twenty-four patients (41.7% males, 58.3% females), mean age 35.3 ± 11.8 years were included. Mean disease duration was 8.3 ± 5.2 years. In median, the patients were previously treated with two biologic agents; however, 25% of the patients were naive to any biologic therapy. Systemic corticosteroids were present in 41.7% patients at baseline and no patient had concomitant biologic or other immunosuppressive therapy. At week 8, 52.9% of patients responded to therapy. Total Mayo decreased in responders from mean 5.9 ± 3.5 to 1.1 ± 1.3 (p = 0.01), while in nonresponders it changed from 8.0 ± 2.5 to 8.9 ± 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 ± 1.0 to 0.6 ± 0.7 (p = 0.02) in responders, however, remained stationary in nonresponders (2.9). CRP and FC dropped significantly in responders (6.7 ± 6.2 vs. 2.0 ± 2.2 mg/l, p = 0.04; 1195 ± 1189 vs. 578 ± 654 μg/g, p = 0.05), but not in nonresponders. The responding and nonresponding groups differed significantly in baseline triglycerides, which were higher in nonresponders. Other baseline parameters were comparable. In responders, there was a significant decrease in IL-4 and no change in IL-10, while in nonresponders, there was no change in IL-4 and a significant decrease in IL-10. Tofacitinib was stopped in 23.5% of patients at week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of CMV colitis, C. diff. colitis and oral candidiasis occurred. Conclusion Tofacitinib was efficient in inducing clinical response with mucosal healing in about 50% of UC patients after 8 weeks of therapy. There was no clear baseline predictor of response, however, considering limited sample, there was also no indication of even multiple biologics failure negatively affecting the response. Preliminary results of cytokine dynamics suggest early IL-4 decrease as a potential biomarker of response, warranting further investigation.
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Rácz, Emőke, and Errol P. Prens. "Molecular pathophysiology of psoriasis and molecular targets of antipsoriatic therapy." Expert Reviews in Molecular Medicine 11 (December 2009). http://dx.doi.org/10.1017/s146239940900129x.
Full textAbstract:
Psoriasis is a chronic inflammatory skin disease characterised by elevated red scaly plaques on specific body sites. Histologically, the plaques are defined by epidermal hyperplasia, epidermal and dermal infiltration by leukocytes, and changes in the dermal microvasculature. Differentiation and activation are disturbed in lesional psoriatic keratinocytes, and the pool of proliferating keratinocytes is increased, which is accompanied by enhanced production of proinflammatory cytokines, adhesion molecules and antimicrobial peptides. These changes in psoriatic keratinocytes are caused by altered expression of genes associated with epidermal differentiation, and by activation of signalling pathways involving signal transducer and activator of transcription 3 (STAT3), type I interferon (IFN) and mitogen-activated protein kinase (MAPK). The number of T cells, and myeloid and plasmacytoid dendritic cells (DCs) is markedly increased in psoriatic lesions. Myeloid DCs produce interleukin (IL)-23, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), which are crucial cytokines in the pathogenesis of psoriasis. IL-23 stimulates the secretion of IL-22 by T helper 17 cells, and IL-22 induces epidermal hyperplasia. The crosstalk between keratinocytes and leukocytes via their proinflammatory cytokines creates the vicious circle of chronic skin inflammation seen in psoriasis. This suggests that optimal treatment of psoriasis needs to target pathogenic pathways in both leukocytes and keratinocytes.
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Lee, Jeongsoo, Nuri Na, and Joonsoo Park. "A Case of Widespread Dermatophytosis during Interleukin-17A Inhibitor Treatment in Psoriasis Patient with Tinea Unguium." Journal of Mycology and Infection, December 31, 2019, 100–104. http://dx.doi.org/10.17966/jmi.2019.24.4.100.
Full textAbstract:
Interleukin-17 (IL-17) is secreted by a class of helper T cells called Th17 cells, which stimulates keratinocytes to secrete proinflammatory mediator and to recruit other inflammatory cells in psoriatic skins. IL-17A inhibitor was approved for the management of psoriatic arthritis by FDA. It is the one of the biologics approved as first-line therapy for the management of psoriasis. But several studies show some side effects of IL-17A inhibitor such as upper respiratory infection and fungal infection like Candida albicans. Herein we report a widespread dermatophytosis during IL-17A inhibitor treatment. A 66-year-old male patient, with tinea unguium and chronic plaque psoriasis for several decades, presented with multiple erythematous scaly macules and patches for 2 weeks. He medicated IL-17A inhibitor for treating psoriasis total 3 times and last injection was 1 week ago. Dermatological examination revealed the involvement of 20% body surface area in the form of erythematous scaly macules and patches. KOH mount revealed the presence of numerous hyphae. The patient was started on oral terbinafine, topical isoconazole and efinaconazole. His skin lesions were improved after 1 month of anti-fungal therapy. IL-17 plays an important role in mucocutaneous microbial defense. So, fungal infection should be checked in using IL-17A inhibitor patients periodically.
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Tsiogkas, Sotirios G., Athanasios Mavropoulos, Efthimios Dardiotis, Efterpi Zafiriou, and Dimitrios P. Bogdanos. "A sharp decrease of Th17, CXCR3 +-Th17 and Th17.1 in peripheral blood is associated with an early anti-IL-17-mediated clinical remission in psoriasis." Clinical and Experimental Immunology, August 4, 2022. http://dx.doi.org/10.1093/cei/uxac069.
Full textAbstract:
Abstract Psoriasis—an immune-mediated skin disease—implicates in its pathophysiology circulating pro-inflammatory cell populations, cytokines, and their interactions with epidermis. The direct effect of approved anti-interleukin- (IL-)17A and anti-IL-17R biologic therapy on immunophenotyping of peripheral blood mononuclear lymphocytes’ (PBMCs) relative sub-population frequencies in psoriasis patients has not yet been described. Using multiparameter flow cytometry we examined T cell subpopulations characterized by CCR6, CCR4 and CXCR3 chemokine receptor surface expression at baseline and after initiation of biologic therapy in PBMCs collected from 30 psoriasis patients. Increased CD3 +CD4 +CXCR3 +, CD3 +CD4 +CCR6 +CCR4 +CXCR3 + (CXCR3 +-Th17) and CD3 +CD4 +CCR6 +CCR4 -CXCR3 + (Th17.1) cell populations were observed in patients with psoriasis in comparison to healthy individuals (n=10). IL-17 therapeutic blockade decreased CD3 +CD4 +CCR6 +, CD3 +CD4 +CXCR3 +, CD3 +CD4 +CCR6 -CXCR3 + (Th1), CD3 +CD4 +CCR6 +CCR4 + (Th17), CD3 +CD4 +CCR6 +CCR4 +CXCR3 + (CXCR3 +-Th17) and CD3 +CD4 +CCR6 +CCR4 -CXCR3 + (Th17.1) cell populations in responding psoriasis patients. Moreover, CD3 +CD4 -CCR6 +, CD3 +CD4 -CXCR3 +, CD3 +CD4 -CCR6 +CCR4 + (Tc17) and CD3 +CD4 -CCR6 -CXCR3 + (Tc1) percentages were also inhibited. Modulation of the same cell sub-populations was also assessed in patients treated with methotrexate (n=4), apremilast (n=4) and anti-IL-23 biologic treatment (n=4). In our study the levels and functional capacity of peripheral pro-inflammatory Th1, Th17 and additional CCR6 + T cell sub-gated populations from psoriasis patients that were treated with anti-IL-17 or anti-IL-17R targeted biologic therapy were explored for the first time. Our data clearly demonstrate that early anti-IL-17 mediated clinical remission is accompanied by a significant decrease of Th1, Th17, CXCR3 +-Th17, and Th17.1 cells.
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Whitley, Sarah K., Mushi Li, Sakeen W. Kashem, Toshiro Hirai, Botond Z. Igyártó, Kelley Knizner, Jonhan Ho, et al. "Local IL-23 is required for proliferation and retention of skin-resident memory T H 17 cells." Science Immunology 7, no. 77 (November 18, 2022). http://dx.doi.org/10.1126/sciimmunol.abq3254.
Full textAbstract:
The cytokine interleukin-23 (IL-23) is critical for development and maintenance of autoimmune inflammation in nonlymphoid tissues; however, the mechanism through which IL-23 supports tissue-specific immunity remains unclear. In mice, we found that circulating memory T cells were dispensable for anamnestic protection from Candida albicans skin infection, and tissue-resident memory (T RM ) cell–mediated protection from C. albicans reinfection required IL-23. Administration of anti–IL-23 receptor antibody to mice after resolution of primary C. albicans infection resulted in loss of CD69 + CD103 + tissue-resident memory T helper 17 (T RM17 ) cells from skin, and clinical anti–IL-23 therapy depleted T RM17 cells from skin of patients with psoriasis. IL-23 receptor blockade impaired T RM17 cell proliferation but did not affect apoptosis susceptibility or tissue egress. IL-23 produced by CD301b + myeloid cells was required for T RM17 maintenance in skin after C. albicans infection, and CD301b + cells were necessary for T RM17 expansion during the development of imiquimod dermatitis. This study demonstrates that locally produced IL-23 promotes in situ proliferation of cutaneous T RM17 cells to support their longevity and function and provides mechanistic insight into the durable efficacy of IL-23 blockade in the treatment of psoriasis.
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Makos, Anaïs, J. H. Kuiper, O. Kehoe, and R. Amarasena. "Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors." Inflammopharmacology, December 12, 2022. http://dx.doi.org/10.1007/s10787-022-01092-x.
Full textAbstract:
AbstractPsoriatic arthritis (PsA) is a chronic and painful inflammatory immune-mediated disease. It affects up to 40% of people with psoriasis and it is associated with several comorbidities such as obesity, diabetes, metabolic syndrome, and hypertension. PsA is difficult to diagnose because of its diverse symptoms, namely axial and peripheral arthritis, enthesitis, dactylitis, skin changes, and nail dystrophy. Different drugs exist to treat the inflammation and pain. When patients do not respond to conventional drugs, they are treated with biologic drugs. Tumour necrosis factor inhibitors (TNFi’s) are commonly given as the first biologic drug; beside being expensive, they also lack efficacy in 50% of patients. A biomarker predicting individual patient’s response to TNFi would help treating them earlier with an appropriate biologic drug. This study aimed to review the literature to identify potential biomarkers that should be investigated for their predictive ability. Several such biomarkers were identified, namely transmembrane TNFα (tmTNF), human serum albumin (HSA) and its half-life receptor, the neonatal Fc receptor (FcRn) which is also involved in IgG lifespan; calprotectin, high mobility group protein B1 (HMGB1) and advanced glycation end products (AGEs) whose overexpression lead to excessive production of pro-inflammatory cytokines; lymphotoxin α (LTα) which induces inflammation by binding to TNF receptor (TNFR); and T helper 17 (Th17) cells which induce inflammation by IL-17A secretion.
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Belpaire, Arno, Nanja van Geel, and Reinhart Speeckaert. "From IL-17 to IFN-γ in inflammatory skin disorders: Is transdifferentiation a potential treatment target?" Frontiers in Immunology 13 (July 28, 2022). http://dx.doi.org/10.3389/fimmu.2022.932265.
Full textAbstract:
The targeted inhibition of effector cytokines such as interleukin 17 (IL-17) in psoriasis and IL-13 in atopic dermatitis offers impressive efficacy with a favorable side effect profile. In contrast, the downregulation of interferon gamma (IFN-γ) in T helper (Th) 1-dominant skin disorders may lead to more adverse events, given the crucial role of IFN-γ in antiviral and antitumoral immunity. Modulating Th17 and Th2 cell differentiation is performed by blocking IL-23 and IL-4, respectively, whereas anti-IL-12 antibodies are only moderately effective in downregulating Th1 lymphocyte differentiation. Therefore, a targeted approach of IFN-γ-driven disorders remains challenging. Recent literature suggests that certain pathogenic Th17 cell subsets with Th1 characteristics, such as CD4+CD161+CCR6+CXCR3+IL-17+IFN-y+ (Th17.1) and CD4+CD161+CCR6+CXCR3+IL-17-IFN-y+ (exTh17), are important contributors in Th1-mediated autoimmunity. Differentiation to a Th17.1 or exTh17 profile results in the upregulation of IFN-y. Remarkably, these pathogenic Th17 cell subsets are resistant to glucocorticoid therapy and the dampening effect of regulatory T cells (Treg). The identification of Th17.1/exTh17 cells in auto-immune disorders may explain the frequent treatment failure of conventional immunosuppressants. In this review, we summarize the current evidence regarding the cellular plasticity of Th17 cells in inflammatory skin disorders. A deeper understanding of this phenomenon may lead to better insights into the pathogenesis of various skin diseases and the discovery of a potential new treatment target.
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Hafkamp, Florianne M. J., Tom Groot Kormelink, and Esther C. de Jong. "Targeting DCs for Tolerance Induction: Don’t Lose Sight of the Neutrophils." Frontiers in Immunology 12 (October 5, 2021). http://dx.doi.org/10.3389/fimmu.2021.732992.
Full textAbstract:
Chronic inflammatory disorders (CID), such as autoimmune diseases, are characterized by overactivation of the immune system and loss of immune tolerance. T helper 17 (Th17) cells are strongly associated with the pathogenesis of multiple CID, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. In line with the increasingly recognized contribution of innate immune cells to the modulation of dendritic cell (DC) function and DC-driven adaptive immune responses, we recently showed that neutrophils are required for DC-driven Th17 cell differentiation from human naive T cells. Consequently, recruitment of neutrophils to inflamed tissues and lymph nodes likely creates a highly inflammatory loop through the induction of Th17 cells that should be intercepted to attenuate disease progression. Tolerogenic therapy via DCs, the central orchestrators of the adaptive immune response, is a promising strategy for the treatment of CID. Tolerogenic DCs could restore immune tolerance by driving the development of regulatory T cells (Tregs) in the periphery. In this review, we discuss the effects of the tolerogenic adjuvants vitamin D3 (VD3), corticosteroids (CS), and retinoic acid (RA) on both DCs and neutrophils and their potential interplay. We briefly summarize how neutrophils shape DC-driven T-cell development in general. We propose that, for optimization of tolerogenic DC therapy for the treatment of CID, both DCs for tolerance induction and the neutrophil inflammatory loop should be targeted while preserving the potential Treg-enhancing effects of neutrophils.
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Hafkamp, Florianne M. J., Tom Groot Kormelink, and Esther C. de Jong. "Targeting DCs for Tolerance Induction: Don’t Lose Sight of the Neutrophils." Frontiers in Immunology 12 (October 5, 2021). http://dx.doi.org/10.3389/fimmu.2021.732992.
Full textAbstract:
Chronic inflammatory disorders (CID), such as autoimmune diseases, are characterized by overactivation of the immune system and loss of immune tolerance. T helper 17 (Th17) cells are strongly associated with the pathogenesis of multiple CID, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. In line with the increasingly recognized contribution of innate immune cells to the modulation of dendritic cell (DC) function and DC-driven adaptive immune responses, we recently showed that neutrophils are required for DC-driven Th17 cell differentiation from human naive T cells. Consequently, recruitment of neutrophils to inflamed tissues and lymph nodes likely creates a highly inflammatory loop through the induction of Th17 cells that should be intercepted to attenuate disease progression. Tolerogenic therapy via DCs, the central orchestrators of the adaptive immune response, is a promising strategy for the treatment of CID. Tolerogenic DCs could restore immune tolerance by driving the development of regulatory T cells (Tregs) in the periphery. In this review, we discuss the effects of the tolerogenic adjuvants vitamin D3 (VD3), corticosteroids (CS), and retinoic acid (RA) on both DCs and neutrophils and their potential interplay. We briefly summarize how neutrophils shape DC-driven T-cell development in general. We propose that, for optimization of tolerogenic DC therapy for the treatment of CID, both DCs for tolerance induction and the neutrophil inflammatory loop should be targeted while preserving the potential Treg-enhancing effects of neutrophils.
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Rosine, Nicolas, and Corinne Miceli-Richard. "Innate Cells: The Alternative Source of IL-17 in Axial and Peripheral Spondyloarthritis?" Frontiers in Immunology 11 (January 8, 2021). http://dx.doi.org/10.3389/fimmu.2020.553742.
Full textAbstract:
Spondyloarthritis (SpA) is a chronic inflammatory rheumatism characterized by inflammation of sacroiliac joints, peripheral joints, and spine. The Assessment of SpondyloArthritis Society describes three disease forms: axial (axSpA), peripheral, and enthesitic SpA. Each may be associated with extra-articular manifestations: psoriasis, inflammatory bowel disease, and acute anterior uveitis. Genome-wide association studies performed in axSpA and psoriatic arthritis (PsA) have shown a shared genetic background, especially the interleukin 23 (IL-23)/IL-17 pathway, which suggests pathophysiological similarities. The convincing positive results of clinical trials assessing the effect of secukinumab and ixekizumab (anti-IL-17A monoclonal antibodies) in axSpA and PsA have reinforced the speculated crucial role of IL-17 in SpA. Nevertheless, and obviously unexpectedly, the differential efficacy of anti-IL-23–targeted treatments between axSpA (failure) and PsA (success) has profoundly disrupted our presumed knowledge of disease pathogeny. The cells able to secrete IL-17, their dependence on IL-23, and their respective role according to the clinical form of the disease is at the heart of the current debate to potentially explain these observed differences in efficacy of IL-23/IL-17–targeted therapy. In fact, IL-17 secretion is usually mainly related to T helper 17 lymphocytes. Nevertheless, several innate immune cells express IL-23 receptor and can produce IL-17. To what extent these alternative cell populations can produce IL-17 independent of IL-23 and their respective involvement in axSpA and PsA are the crucial scientific questions in SpA. From this viewpoint, this is a nice example of a reverse path from bedside to bench, in which the results of therapeutic trials allow for reflecting more in depth on the pathophysiology of a disease. Here we provide an overview of each innate immunity-producing IL-17 cell subset and their respective role in disease pathogeny at the current level of our knowledge.
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Rosine, Nicolas, and Corinne Miceli-Richard. "Innate Cells: The Alternative Source of IL-17 in Axial and Peripheral Spondyloarthritis?" Frontiers in Immunology 11 (January 8, 2021). http://dx.doi.org/10.3389/fimmu.2020.553742.
Full textAbstract:
Spondyloarthritis (SpA) is a chronic inflammatory rheumatism characterized by inflammation of sacroiliac joints, peripheral joints, and spine. The Assessment of SpondyloArthritis Society describes three disease forms: axial (axSpA), peripheral, and enthesitic SpA. Each may be associated with extra-articular manifestations: psoriasis, inflammatory bowel disease, and acute anterior uveitis. Genome-wide association studies performed in axSpA and psoriatic arthritis (PsA) have shown a shared genetic background, especially the interleukin 23 (IL-23)/IL-17 pathway, which suggests pathophysiological similarities. The convincing positive results of clinical trials assessing the effect of secukinumab and ixekizumab (anti-IL-17A monoclonal antibodies) in axSpA and PsA have reinforced the speculated crucial role of IL-17 in SpA. Nevertheless, and obviously unexpectedly, the differential efficacy of anti-IL-23–targeted treatments between axSpA (failure) and PsA (success) has profoundly disrupted our presumed knowledge of disease pathogeny. The cells able to secrete IL-17, their dependence on IL-23, and their respective role according to the clinical form of the disease is at the heart of the current debate to potentially explain these observed differences in efficacy of IL-23/IL-17–targeted therapy. In fact, IL-17 secretion is usually mainly related to T helper 17 lymphocytes. Nevertheless, several innate immune cells express IL-23 receptor and can produce IL-17. To what extent these alternative cell populations can produce IL-17 independent of IL-23 and their respective involvement in axSpA and PsA are the crucial scientific questions in SpA. From this viewpoint, this is a nice example of a reverse path from bedside to bench, in which the results of therapeutic trials allow for reflecting more in depth on the pathophysiology of a disease. Here we provide an overview of each innate immunity-producing IL-17 cell subset and their respective role in disease pathogeny at the current level of our knowledge.