Literatura académica sobre el tema "IL-17 members"

Abstract The interleukin-17 (IL-17) family consists of six family members (IL-17A–IL-17F) and all the corresponding receptors have been identified recently. This family is mainly involved in the host defense mechanisms against bacteria, fungi and helminth infection by inducing cytokines and chemokines, recruiting neutrophils, inducing anti-microbial proteins and modifying T-helper cell differentiation. IL-17A and some other family cytokines are also involved in the development of psoriasis, psoriatic arthritis and ankylosing spondylitis by inducing inflammatory cytokines and chemokines, and antibodies against IL-17A as well as the receptor IL-17RA are being successfully used for the treatment of these diseases. Involvement in the development of inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and tumors has also been suggested in animal disease models. In this review, we will briefly review the mechanisms by which IL-17 cytokines are involved in the development of these diseases and discuss possible treatment of inflammatory diseases by targeting IL-17 family members.

Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike the other members of this family, IL-25 promotes T helper (Th) 2 responses. We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17–producing T cells. We have generated IL-25–deficient (il25−/−) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE). The accelerated disease in the il25−/− mice is associated with an increase of IL-23 in the periphery and a subsequent increase in the number of inflammatory IL-17–, IFNγ-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFNγ in il25−/− mice prevented EAE, suggesting that IL-17 is a major disease-promoting factor. IL-25 treatment at several time points during a relapse-remitting model or chronic model of EAE completely suppressed disease. IL-25 treatment induced elevated production of IL-13, which is required for suppression of Th17 responses by direct inhibition of IL-23, IL-1β, and IL-6 expression in activated dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity.

The IL-17 family is an evolutionarily old cytokine family consisting of six members (IL-17A through IL-17F). IL-17 family cytokines signal through heterodimeric receptors that include the shared IL-17RA subunit, which is widely expressed throughout the body on both hematopoietic and nonhematopoietic cells. The founding family member, IL-17A, is usually referred to as IL-17 and has received the most attention for proinflammatory roles in autoimmune diseases like psoriasis. However, IL-17 is associated with a wide array of diseases with perhaps surprisingly variable pathologies. This review focuses on recent advances in the roles of IL-17 during health and in disease pathogenesis. To decipher the functions of IL-17 in diverse disease processes it is useful to first consider the physiological functions that IL-17 contributes to health. We then discuss how these beneficial functions can be diverted toward pathogenic amplification of deleterious pathways driving chronic disease.

Background and Objectives: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. Materials and Methods: In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23–IL-17 axis, by reporting updated findings from the scientific literature. Results: Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). Conclusions: IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.

Abstract IL-17 producing Th17 has a key role in the pathogenesis of autoimmune inflammation. Among various cytokines which are interwoven with the IL-17 pathway, members of IL-1beta family including IL-18 have recently gained significance. In the present study, we stimulated synovial fibroblasts with the combination of IL-17 and IL-18, and quantified the cellular production of stromal cell-derived factor-1 (SDF-1) with ELISA and its mRNA with RT-PCR. Both IL-17 and IL-18 significantly increased the level of SDF-1, not only individually but also synergistically (p<0.05). The synergism was effectively suppressed by anti-IL-17, anti-IL-18 antibodies and PI3K inhibitor. In conclusion, PI3K-dependent synergism between IL-18 and IL-17 is first observed in this study, and adds a novel perspective for the role of IL-18 in immune regulation. The two cytokines’ individual effects, mutual interaction and synergism draw a crisscrossing map between IL-1 family and IL-17.

Members of the interleukin 12 (IL-12) family have been known to be inflammatory factors since their discovery. The IL-12 family consists of IL-12, IL-23, IL-27, IL-35, and a new member, IL-39, which has recently been identified and has not yet been studied extensively. Current literature has described the mechanisms of immunity of these cytokines and potential uses for therapy and medical cures. IL-12 was found first and is effective in combatting a wide range of naturally occurring viral infections through the upregulation of various cytokines to clear the infected cells. IL-23 has an essential function in immune networks, can induce IL-17 production, and can antagonize inhibition from IL-12 in the presence of T helper (Th) 17 cells, resulting in type II IFN (IFN-γ) regulation. IL-27 has a competitive relationship to IL-35 because they both include the same subunit, the Epstein–Barr virus-induced gene3 (EBi3). This review provides a simple introduction to the IL-12 family and focuses on their functions relevant to their actions to counteract viral infections.

L’ozone est un des polluants présents dans l’air que nous respirons. Les pics de ce polluant entrainent une augmentation des hospitalisations et des cas d’exacerbations d’asthme allergique. L’objectif de ce travail est d’étudier plus en détails les mécanismes inflammatoires mis en place après exposition à l’ozone. Cette étude s’est déroulée en trois axes, les deux premiers traitant du rôle de deux alarmines, l’IL-33 et l’IL-1α et le troisième se focalisant sur AhR, un récepteur impliqué dans la réponse à de nombreux polluants. Pour ce faire, des souris ont été exposées à l’ozone selon deux modèles, l’un aigu et l’autre chronique, puis les paramètres inflammatoires, le dommage tissulaire et les difficultés respiratoires ont été évalués. Nous montrons ici qu’une exposition aigüe à l’ozone induit la libération de molécules comme l’IL-33 et l’IL-1α. L’IL-33 agit au niveau de la barrière épithéliale, où elle permet l’expression et le maintien des jonctions serrées, qui sont augmentées en réponse à la pollution à l’ozone. L’IL-33 régule également l’infiltration des neutrophiles, alors que l’IL-1α l’induit. Ensuite nous avons montré que le récepteur AhR est activé après exposition chronique à l’ozone. AhR semble réguler la production de cytokines telles que l’IL-17A et l’IL-22 et ainsi protège d’une trop forte réponse inflammatoire. Pour conclure, nous avons montré que la production d’IL-33 et l’activation du récepteur AhR étaient nécessaires pour contrôler l’inflammation induite par l’ozone, alors que la production d’IL-1α l’induisait. Cette étude aura permis de mettre en évidence de potentielles cibles thérapeutiques pour soulager les maux provoqués par la pollution
Ozone is a common ambient air polluant. Ozone peaks induce increase of asthma exacerbation, respiratory distress, emergencies and hospital admissions. The aim of this thesis project is to dissect inflammatory mechanisms induced after ozone exposure. This study is conducted according three axes, the first two dealing with the roles of two alarmines, IL-1α and IL-33 and the third is focused on the role of aryl hydrocarbon receptor (AhR), a receptor involved in several pollutant responses. Acute and chronic experimental models of ozone exposure were used to evaluate inflammatory parameters in lung, tissue damage and airway hyperresponsiveness. Here we show that acute ozone exposure induces IL-1α and IL-33 release. IL-33 acts on lung epithelial barrier, allowing the expression and maintenance of tight junctions induced after ozone exposure. Moreover, IL-33 represses neutrophils infiltration while IL-1α induces it. Furthermore we show that AhR is activated after chronic ozone exposure. AhR regulates cytokines production such as IL-17A and IL-22 and plays a protective role against higher inflammation. Overall, IL-33 production and AhR activation are necessary to control ozone-induced inflammation, in contrast to IL-1α. These findings highlight potential therapeutic targets for the treatment of lung inflammation following ozone exposure

Chagas disease, caused by the protozoan Trypanosoma cruzi, is characterized by an acute phase followed by a chronic phase. Most patients in the chronic phase do not present any clinical signs being clinically classified as indeterminate. On the other hand, about 30% of the patients develop the symptomatic clinical forms (cardiac and/or digestive), and the chronic chagasic cardiomyopathy (CCC) is the most severe form of Chagas disease. The wide variation in clinical presentation of chagasic patients allow us to hypothesize that genetic factors related to the host, particularly genetic polymorphisms, may be responsible, at least in part, by the interindividual differences in the response to the infection. Thus, the present study aimed to assess possible associations between single nucleotide polymorphisms of genes encoding the IL-1, IL-1, IL-1ra, IL-17A and IL-17F and the susceptibility to the development of CCC in Brazilian patients from Minas Gerais. The genotyping of IL1A (-889C/T), IL1B (+3954C/T), IL1RN (+2018T/C), IL17A (-197A/G) e IL17F (+7488T/C) polymorphisms was performed in a sample of 109 patients with CCC and 59 with the indeterminate form, using Real Time PCR. The plasmatic levels of IL-1 were obtained from 20 patients using ELISA reaction. Patients carrying the T variant for IL-1 e IL-1 have two times more chance of developing the cardiac form as compared to the indeterminate form (IL-1:OR=2,01; CI=1,06-3,82; p=0,032; IL-1:OR=2,53; CI=1,18-5,42; p=0,015). The same was observed when we analyzed the allelic frequency (IL-1:OR=1,67; CI=1,01-2,77; p=0,043; IL-1:OR=2,16; CI=1,11-4,19; p=0,020). On the other hand, the heterozygote genotype (TC) of IL-1ra (antagonist receptor of IL-1) was associated with the indeterminate form (OR=2,27; CI=1,02-5,04; p=0,042). Multivariate analysis combining SNPs of IL-1 cluster demonstrated that patients with a more pro-inflammatory profile (carriers of the T variant for both IL-1 and IL-1) have greater chance of developing CCC (OR=3,14; CI=1,35-7,32; p=0,008). No difference was observed in the plasmatic levels of IL-1 between indeterminate and dilated cardiac patients. The study of IL-17A showed that carriers of the A- genotype (GG) have two times more chance of developing the cardiac form as compared with the indeterminate form (OR=2,08; CI=1,08-4,00; p=0.027). A similar result was observed for the allelic frequency (OR=1,71; CI=1,00-2,91; p=0.048). For the IL-17F polymorphism, no association with different forms of Chagas disease was found in the population under study. In summary, our results showed that polymorphisms in IL-1 family and IL-17A genes are associated with different clinical outcomes of Chagas disease
A doença de Chagas é causada pelo protozoário Trypanosoma cruzi e caracteriza-se por uma fase aguda, seguida de uma fase crônica. Na fase crônica, a maioria dos pacientes não apresenta sinais clínicos da doença, sendo classificados como indeterminados. Entretanto, cerca de 20-30% desenvolvem a forma sintomática da doença (cardíaca e/ou digestiva), sendo a cardiomiopatia chagásica crônica (CCC) a forma mais grave da doença de Chagas. A ampla variação no quadro clínico de pacientes chagásicos permite hipotetizar que fatores genéticos relacionados ao hospedeiro, em especial os polimorfismos genéticos, possam ser responsáveis, em parte, pelas diferenças interindividuais de resposta à infecção pelo patógeno. Nesse sentido, o presente trabalho teve como objetivo principal avaliar possíveis associações entre polimorfismos de nucleotídeo único (SNPs) de genes codificadores das interleucinas IL-1, IL-1, IL-1ra, IL-17A e IL-17F e a suscetibilidade ao desenvolvimento de CCC em pacientes brasileiros provenientes do estado de Minas Gerais. As genotipagens dos polimorfismos IL1A (-889C/T), IL1B (+3954C/T), IL1RN (+2018T/C), IL17A (-197A/G) e IL17F (+7488T/C) foram realizadas em uma amostra de 109 pacientes com CCC e 59 indeterminados, usando a técnica de PCR em tempo real Os níveis plasmáticos da citocina IL-1 foram obtidos de 20 pacientes por meio de reações de ELISA. Pacientes portadores da variante alélica T para IL-1 e IL-1 possuem duas vezes mais chance de desenvolver a forma cardíaca quando comparados com a forma indeterminada (IL-1: OR=2,01; IC=1,06-3,82; p=0,032; IL-1: OR=2,53; IC=1,18-5,42; p=0,015). O mesmo foi observado quando se comparou a frequência da variante alélica T (IL-1:OR=1,67; IC=1,01-2,77; p=0,043; IL-1:OR=2,16; IC=1,11-4,19; p=0,020). Por outro lado, a ocorrência do genótipo heterozigoto (TC) da IL-1ra (antagonista de receptor da IL-1) apresentou associação com a forma clínica indeterminada (OR=2,27; IC=1,02-5,04; p=0,042). As análises multivariadas no cluster da IL-1 demonstraram que pacientes com perfil mais pró-inflamatório (portadores das variantes T para IL-1 e IL-1) possuem ainda maior chance de desenvolver a CCC (OR=3,14; IC=1,35-7,32; p=0,008). Entretanto, não houve diferenças estatisticamente significativas nos níveis plasmáticos da IL-1 entre os grupos de pacientes indeterminado e cardíaco dilatado.Em relação aos polimorfismos nos genes que codificam para IL-17, o estudo da IL-17A revelou que os portadores do genótipo A- (GG) possuem duas vezes mais chance de desenvolver a forma cardíaca quando comparados com a indeterminada (OR=2,08; IC=1,08-4,00; p=0,027). Resultado similar foi observado em relação à frequência alélica (OR=1,71; IC=1,00-2,91; p=0,048). Em relação ao polimorfismo da IL-17F, não foi encontrada nenhuma associação com as diferentes formas da doença de Chagas na população estudada. Os resultados indicam que polimorfismos em genes da família IL-1 e da IL-17A estão associados com diferentes cursos clínicos da doença de Chagas.

Neutrophils are known to perform a series of effector functions that are crucial for the innate and adaptive responses towards infections. Furthermore, neutrophils respond to various stimuli, including microbial components, by synthetizing and secreting a variety of cytokines. In this context, the main objective of this study was to re-evaluate the capacity of human neutrophils to express and produce cytokines of the IL-17 family, including IL-17A, IL-17B, IL-17F and IL-17AF since the current literature on this topic is discordant. By performing RT-qPCR, immunohistochemistry (IHC), immunoblotting, protein measurement via commercial ELISA, chromatin immunoprecipitation (ChIP) and ChIP-seq, we evaluated transcriptional and epigenetic regulation, as well as production of the latter cytokines by highly pure (> 99.7 %) populations of human neutrophils. In agreement with some published data, we found that neutrophils do not express/produce IL-17A, IL-17F, IL-17AF or IL-17B mRNA/protein upon incubation with a variety of agonists. Similar findings were observed by analyzing neutrophils obtained from active psoriatic patients. No IL-17A and IL-17F mRNA expression/production was found even when human neutrophils from healthy donors were incubated with IL-6 plus IL-23 at very elevated concentrations in combination with inactivated hyphae or conidia from Aspergillus fumigatus, unlike shown in multiple studies. Moreover, consistent with the inability of human neutrophils to express IL-17A and IL-17F mRNA, no deposition of H3K27Ac and H3K4me1, which are histone marks of, respectively, active and poised genomic regulatory elements, was detected at the IL-17A/F genomic locus in resting or IL-6 plus IL-23-stimulated neutrophils. In addition, although we found that anti-IL-17A and anti-IL-17B commercial antibodies positively stained cytospin preparations of resting and activated neutrophils by IHC, these antibodies do not recognize any intracellular protein having the correct MW of either IL-17A or IL-17B in corresponding lysates of the same neutrophil preparations by immunoblotting. Since the same antibodies were found to strongly stain other intracellular proteins of neutrophils, we conclude that their ability to positively stain neutrophils derives from IL-17A- or IL-17B-independent unspecific binding. In conclusion, our data not only confirm and further support our previous original findings on the inability of human neutrophils to express/produce IL-17A, IL-17B and IL-17F mRNAs/proteins, but also attempt to explain why other published studies continue to report the opposite.

Immunotherapies targeting interleukin 17 (IL-17) have a strong effect on plaque psoriasis. However, many previous studies on IL-17 focused only on the T-helper 17 (Th17) immune response, and a few studies have reported that IL-17A may affect psoriatic epidermal structure. IL-17 includes six family members, namely IL-17A–F, which are involved in a wide variety of biological responses. IL-17A is produced mainly by Th17 cells or group 3 innate lymphoid cells (ILC3), while IL-17C is locally produced by epithelial cells, such as keratinocytes. In contrast to IL-17C, which is locally produced in various cells such as keratinocytes, it is predicted that IL-17A, which is produced by limited cells and has systemic effects, has different roles in epidermal development. For example, several research studies have shown that IL-17A affects terminal differentiation of epidermis by suppressing the expression of filaggrin or loricrin in keratinocytes. On the other hand, IL-17C, which is produced by keratinocytes themselves, does not have as strong as an effect on epidermal development as IL-17A. In this chapter, we summarized the effects of IL-17A and other IL-17 members on epidermal development and their comprehensive roles based on previously reported papers.

Human Interlekin-17 is produced by memory activated CD4+ T cells and other cells. It was initially considered unique in that its specific receptor is distinct from other cytokine receptors. IL-17 receptor is ubiquitously expressed by different cells including T cells. IL-17 plays a role in regulating growth, immune response and pro-inflammatory responses. It regulates differentiation of a subset of Th0 cells into Th-17 cells, which produce IL-17-induced cytokines. The IL-17R belongs to type 1 cytokine receptors. IL-17 belongs to a superfamily of its own, which includes IL-17A, IL-17B, IL-17C, IL-17E and IL-17F. These members of IL-17 superfamily have some sequence homology but bind to different receptors. Prior to this investigation, limited information existed on the effects of IL-17A in human leukemia cell lines. Our results show that IL-17A promotes growth, anti-apoptotic effects, chemotaxis, cytokine expression and transcriptional factor activation in leukemia cells. IL-17A activates multiple signaling pathways including PI-3 K, Jak–STAT, Raf-ERK1/2 and SRC kinase pathways, which mediate different biological effects of IL-17A in leukemia cells. Our findings implicate IL-17A in leukemia cell growth and survival, supporting potential leukemia therapy via development of anti-IL-17A drugs. This chapter focuses on IL-17A, herein referred to as IL-17.