Academic literature on the topic 'CXCL12/CXCR4 axi'
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Journal articles on the topic "CXCL12/CXCR4 axi"
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Tao, Zhengang, Ying Yuan, and Qingwu Liao. "Alleviation of Lipopolysaccharides-Induced Acute Lung Injury by MiR-454." Cellular Physiology and Biochemistry 38, no. 1 (2016): 65–74. http://dx.doi.org/10.1159/000438609.
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Background/Aims: Although acute lung injury (ALI) is an important and common disease in humans, its pathogenesis is poorly understood and its therapeutic outcome has not been significantly improved in the past years. Here, we examined whether application of microRNAs might inhibit the ALI-associated lung inflammatory, and subsequently reduce the injury. Methods: In vitro, we performed bioinformatics analyses to identify the miRNAs that target the most important chemo-attractive factor CXCL12, and confirmed that the binding was functional by luciferase reporter assay. We prepared adeno-associated virus (AAV) carrying miRNA mimics or null control. We expressed miRNA in mouse lung through i.v. injection of AAV and then we used Lipopolysaccharides (LPS) to induce ALI in mice. We analyzed the changes in permeability index and production of inflammatory cytokines in mouse lung, and we also verified the effects of virus-mediated gene expression by examining the levels of miRNAs and CXCL12 in lung by RT-qPCR and ELISA, and by quantifying the recruited inflammatory cells in mouse lung by flow cytometry. Results: We found that miR-454 targeted the 3'-UTR of CXCL12 mRNA to inhibit its protein translation in human lung epithelial cells. Overexpression of miR-454 in mouse lung significantly reduced the LPS-induced increases in permeability index and production of inflammatory cytokines CXCL1, CXCL2, IL6 and TNFα, possibly through suppression of CXCL12/CXCR4-mediated recruitment of inflammatory cells. Conclusion: Overexpression of miR-454 in lung may be a promising therapeutic approach to reduce the severity of ALI.
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Yao, Miao-En, Yi Huang, Qing-Qing Dong, Yi Lu, and Wei Chen. "The Renshen Chishao Decoction Could Ameliorate the Acute Lung Injury but Could Not Reduce the Neutrophil Extracellular Traps Formation." Evidence-Based Complementary and Alternative Medicine 2022 (August 29, 2022): 1–16. http://dx.doi.org/10.1155/2022/7784148.
Full textAbstract:
The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2 antagonist group, and ALI + CXCR2 antagonist group. We estimated the lung injury by the hematoxylin and eosin staining, the neutrophil extracellular traps (NETs) formations by the immunofluorescence colocalization and enzyme-linked immunosorbent assay (ELISA), and the CXCR2/CXCL2 pathway by the flow cytometry, ELISA, and real-time polymerase chain reaction. We conducted the high-throughput sequencing and enrichment analyses to explore the potential mechanisms. The results showed that the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung injury and inflammatory response but failed to reduce the circulating and lung tissue NETs formation and the blood neutrophil percent. The high-dose RC decoction increased the plasma CXCL2 level, but the RC decoction had no effects on the neutrophilic CXCR2 levels. Under the inhibition of the CXCR2, the middle-dose RC decoction still decreased the lung injury score but as yet had unobvious influence on the NETs formation. Other potential mechanisms of the RC decoction against the ALI involved the pathways of ribosome and coronavirus disease 2019 (COVID-19); the target genes of inflammatory factors, such as Ccl17, Cxcl17, Cd163, Cxcr5, and Il31ra, and lncRNAs; and the regulations of the respiratory cilia. In conclusion, the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung inflammatory injury via upregulating the CXCL2/CXCR2 pathway but could not reduce the circulating or lung tissue NETs formation.
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Huang, Fei, Yunyi Lan, Liyue Qin, Huaihuai Dong, Hailian Shi, Hui Wu, Qinrui Zou, Zhibi Hu, and Xiaojun Wu. "Astragaloside IV Promotes Adult Neurogenesis in Hippocampal Dentate Gyrus of Mouse through CXCL1/CXCR2 Signaling." Molecules 23, no. 9 (August 29, 2018): 2178. http://dx.doi.org/10.3390/molecules23092178.
Full textAbstract:
Astragaloside IV (ASI) has been reported to promote neural stem cells proliferation in vitro and CXCR2 expression on neutrophils. The present study was aimed to investigate the influence of ASI on adult neurogenesis in hippocampal dentate gyrus (DGs) of mouse and to discuss the possible underlying mechanisms. Total number of proliferative cells (BrdU+), pre-mature neurons (DCX+), early proliferative cells (BrdU+/DCX+), proliferative radial gila-like cells (BrdU+/GFAP+) and newly generated neurons (BrdU+/NeuN+) after ASI or vehicle administration for two weeks were counted, respectively. The results showed that BrdU+ cells and DCX+ cells were significantly increased in DGs of mice administered with ASI. The numbers of BrdU+/DCX+, BrdU+/GFAP+ cells and BrdU+/NeuN+ cells were also elevated in the ASI group. Correspondingly, ASI increased the protein expression of hippocampal DCX, GFAP and NeuN. Further study disclosed that ASI remarkably up-regulated the mRNA and protein expressions of CXCL1 as well as that of CXCR2 in the hippocampus. The promotive effect of ASI on DCX, GFAP and NeuN protein expression was abolished by SB225002, the inhibitor of CXCR2. Our results indicated that ASI modulated the homeostasis of the CXCL1/CXCR2 signaling pathway, which might be responsible for the increased neurogenesis within the hippocampal DGs of mice.
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Ahuja, Nilesh, Ana Andres-Hernando, Christopher Altmann, Rhea Bhargava, Jasna Bacalja, Ryan G. Webb, Zhibin He, Charles L. Edelstein, and Sarah Faubel. "Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice." American Journal of Physiology-Renal Physiology 303, no. 6 (September 15, 2012): F864—F872. http://dx.doi.org/10.1152/ajprenal.00025.2012.
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Serum IL-6 is increased in patients with acute kidney injury (AKI) and is associated with prolonged mechanical ventilation and increased mortality. Inhibition of IL-6 in mice with AKI reduces lung injury associated with a reduction in the chemokine CXCL1 and lung neutrophils. Whether circulating IL-6 or locally produced lung IL-6 mediates lung injury after AKI is unknown. We hypothesized that circulating IL-6 mediates lung injury after AKI by increasing lung endothelial CXCL1 production and subsequent neutrophil infiltration. To test the role of circulating IL-6 in AKI-mediated lung injury, recombinant murine IL-6 was administered to IL-6-deficient mice. To test the role of CXCL1 in AKI-mediated lung injury, CXCL1 was inhibited by use of CXCR2-deficient mice and anti-CXCL1 antibodies in mice with ischemic AKI or bilateral nephrectomy. Injection of recombinant IL-6 to IL-6-deficient mice with AKI increased lung CXCL1 and lung neutrophils. Lung endothelial CXCL1 was increased after AKI. CXCR2-deficient and CXCL1 antibody-treated mice with ischemic AKI or bilateral nephrectomy had reduced lung neutrophil content. In summary, we demonstrate for the first time that circulating IL-6 is a mediator of lung inflammation and injury after AKI. Since serum IL-6 is increased in patients with either AKI or acute lung injury and predicts prolonged mechanical ventilation and increased mortality in both conditions, our data suggest that serum IL-6 is not simply a biomarker of poor outcomes but a pathogenic mediator of lung injury.
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Zuk, A., M. Gershenovich, Y. Ivanova, R. T. MacFarland, S. P. Fricker, and S. Ledbetter. "CXCR4 antagonism as a therapeutic approach to prevent acute kidney injury." American Journal of Physiology-Renal Physiology 307, no. 7 (October 1, 2014): F783—F797. http://dx.doi.org/10.1152/ajprenal.00685.2013.
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We examined whether antagonism of the CXCR4 receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCR4 is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSCs). Plerixafor (AMD3100, Mozobil) is a small-molecule CXCR4 antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion. Serum creatinine and blood urea nitrogen were significantly reduced 24 h after reperfusion, as were tissue injury and cell death. Plerixafor prevented the renal increase in the proinflammatory chemokines CXCL1 and CXCL5 and the cytokine IL-6. Flow cytometry of kidney homogenates confirmed the presence of significantly fewer leukocytes with plerixafor treatment; additionally, myeloperoxidase activity was reduced. AMD3465, a monocyclam analog of plerixafor, was similarly renoprotective. Four weeks postreperfusion, long-term effects included diminished fibrosis, inflammation, and ongoing renal injury. The mechanism by which CXCR4 inhibition ameliorates AKI is due to modulation of leukocyte infiltration and expression of proinflammatory chemokines/cytokines, rather than a HSC-mediated effect. The data suggest that CXCR4 antagonism with plerixafor may be a potential option to prevent AKI.
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Liu, Sheng, Jian Tang, Lei Huang, Qirong Xu, Xiang Ling, and Jichun Liu. "Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through miRNAs-Mediated CXCR2 Inhibition." Cellular Physiology and Biochemistry 36, no. 5 (2015): 2003–11. http://dx.doi.org/10.1159/000430168.
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Background/Aims: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are lethal diseases in humans, and the current treatments have limited therapeutic effects. Cordyceps militaris (CM) is a caterpillar-grown traditional medicinal mushroom, and has been used as a natural invigorant for longevity, endurance, and vitality in China. Recently, purified extracts from CM have been shown to have beneficial effects on various diseases including cancer. Nevertheless, a role of CM in ALI has not been examined previously. Methods: Here, we used a bleomycin-induced ALI model to study the effects of CM on the severity of ALI in mice. The levels of CXCR2, a receptor for Interleukin 8 (IL-8) in pulmonary microvascular endothelial cells, were examined in different experimental groups. The levels of microRNA (miR)-1321 and miR-3188 were also examined in lung samples and in CM. Adeno-associated viruses carrying miR-1321 and miR-3188 were injected into bleomycin-treated mice for evaluation their effects on the severity of ALI. Results: CM treatment significantly alleviated the severity of bleomycin-induced ALI in mice. The increases in lung CXCR2 by bleomycin were significantly reduced by CM at protein level, but not at mRNA level. CM contained high levels of 2 miRNAs (miR-1321 and miR-3188) that target 3'-UTR of CXCR2 mRNA to inhibit its expression. Overexpression of miR-1321 and miR-3188 in mouse lung through AAV-mediated gene therapy mimicked the effects of CM. Conclusion: CM may alleviate severity of murine ALI through miRNAs-mediated CXCR2 inhibition.
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Holloman, Bryan L., Mitzi Nagarkatti, and Prakash Nagarkatti. "Pulmonary macrophage activation and recruitment in lipopolysaccharide-induced acute lung injury mediates neutrophil infiltration: Role of AhR ligation in intervention." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 105.36. http://dx.doi.org/10.4049/jimmunol.208.supp.105.36.
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Abstract CCL2-CCR2 signaling plays an essential role in the recruitment of macrophages and neutrophils following tissue injury. During inflammation, CCR2+ macrophage secretion of CCL2 induces an autocrine effect that leads to an intracellular signaling cascade of macrophages that promotes upregulation of CCL2, CXCL2, and CXCL3 expression, which stimulates the chemotaxis of blood circulating CCR2+ monocytes and CXCR2+ neutrophils to the disease site. Interestingly, the aryl hydrocarbon receptor (AhR) ligand has been shown to regulate effector cell recruitment. Therefore, we studied the effects of the AhR ligand, indole-3-carbinol (I3C) on the recruitment of circulating CCR2+ monocytes and CXCR2+ neutrophils during acute lung injury (ALI). To induce ALI in C57BL/6 mice and Ccr2gfp mice (mice deficient in the CCR2 receptor), they were given 5mg/kg of lipopolysaccharide intranasally. Mice were treated with I3C or vehicle following disease induction. Interestingly, I3C downregulated neutrophils expressing CXCR2 (a receptor associated with neutrophil recruitment) and CCR2+ macrophages in lungs of C57BL/6 diseased-mice. Furthermore, to determine if CCR2+ macrophages recruit CXCR2+ neutrophils, we induced ALI in Ccr2gfp mice. Abolishing the expression of CCR2 eliminated the recruitment of CXCR2+ neutrophils to the lungs during ALI. Interestingly, scRNASeq of macrophage/monocyte cells showed that I3C reduced expression of CXCL3. CXCL3 gene translates into the chemokine CXCL3, which binds to CXCR2 and is involved in neutrophil recruitment to the disease site. These findings suggest that CCR2 macrophages are involved in the recruitment of CXCR2+ neutrophils, and the AhR ligand I3C can regulate immune cell trafficking capabilities. Supported by NIH grants P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI123947, R01AI160896 and R01AI123947-S2
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Su, Vincent Yi-Fong, Wei-Chih Chen, Wen-Kuang Yu, Huai-Hsuan Wu, Hao Chen, and Kuang-Yao Yang. "Nintedanib Regulates GRK2 and CXCR2 to Reduce Neutrophil Recruitment in Endotoxin-Induced Lung Injury." International Journal of Molecular Sciences 22, no. 18 (September 13, 2021): 9898. http://dx.doi.org/10.3390/ijms22189898.
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The role of nintedanib, a multiple tyrosine kinase inhibitor, in the treatment of sepsis-induced acute lung injury (ALI) remains unclear. Lipopolysaccharide (LPS), also known as endotoxin, has been used to induce ALI. The goal of this study was to assess the effect of nintedanib in attenuating the histopathological changes of LPS-induced ALI. Nintedanib was administered via oral gavage to male C57BL/6 mice 24 h and 10 min before intratracheal endotoxin instillation. Lung histopathological characteristics, adhesion molecule expression, and the regulatory signaling pathways of neutrophil chemotaxis were analyzed after 24 h. We found that nintedanib significantly reduced histopathological changes and neutrophil recruitment in LPS-induced ALI. The number of neutrophils in bronchoalveolar lavage fluid (BALF) was reduced in nintedanib-treated relative to untreated mice with ALI. Nintedanib mediated the downregulation of the chemotactic response to LPS by reducing the expression of adhesion molecules and the phosphorylated p38:total p38 mitogen-activated protein kinase (MAPK) ratio in the lungs of mice with ALI. Nintedanib also reduced the expression of lymphocyte antigen 6 complex locus G6D (Ly6G) and very late antigen 4 (VLA-4) in BALF neutrophils and mediated the downregulation of chemokine (C-X-C motif) receptor 2 (CXCR2) and upregulation of G protein-coupled receptor kinase 2 (GRK2) activity in peripheral blood neutrophils in mice with LPS-induced ALI. Nintedanib improved the histopathological changes of LPS-induced ALI by reducing neutrophil chemotaxis. These effects were mediated by the inhibition of adhesion molecules via the activation of GRK2 and the inhibition of p38 MAPK and CXCR2.
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Iwakura, Takamasa, Zhibo Zhao, Julian A. Marschner, Satish Kumar Devarapu, Hideo Yasuda, and Hans Joachim Anders. "Dipeptidyl peptidase-4 inhibitor teneligliptin accelerates recovery from cisplatin-induced acute kidney injury by attenuating inflammation and promoting tubular regeneration." Nephrology Dialysis Transplantation 34, no. 10 (January 8, 2019): 1669–80. http://dx.doi.org/10.1093/ndt/gfy397.
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AbstractBackgroundCisplatin is an effective chemotherapeutic agent. However, acute kidney injury (AKI) and subsequent kidney function decline limits its use. Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to attenuate kidney injury in some in vivo models, but the mechanisms-of-action in tubule recovery upon AKI remain speculative. We hypothesized that DPP-4 inhibitor teneligliptin (TG) can facilitate kidney recovery after cisplatin-induced AKI.MethodsIn in vivo experiment, AKI was induced in rats by injecting 5 mg/kg of cisplatin intravenously. Oral administration of 10 mg/kg of TG, once a day, was started just before injecting cisplatin or from Day 5 after cisplatin injection. In an in vitro experiment, proliferation of isolated murine tubular cells was evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and cell counting. Cell viability was analysed by MTT assay or lactate dehydrogenase (LDH) assay.ResultsIn in vivo experiments, we found that TG attenuates cisplatin-induced AKI and accelerates kidney recovery after the injury by promoting the proliferation of surviving epithelial cells of the proximal tubule. TG also suppressed intrarenal tumour necrosis factor-α expression, and induced macrophage polarization towards the anti-inflammatory M2 phenotype, both indirectly endorsing tubule recovery upon cisplatin injury. In in vitro experiments, TG directly accelerated the proliferation of primary tubular epithelial cells. Systematic screening of the DPP-4 substrate chemokines in vitro identified CXC chemokine ligand (CXCL)-12 as a promoted mitogenic factor. CXCL12 not only accelerated proliferation but also inhibited cell death of primary tubular epithelial cells after cisplatin exposure. CXC chemokine receptor (CXCR)-4 antagonism abolished the proliferative effect of TG.ConclusionsThe DPP-4 inhibitor TG can accelerate tubule regeneration and functional recovery from toxic AKI via an anti-inflammatory effect and probably via inhibition of CXCL12 breakdown. Hence, DPP-4 inhibitors may limit cisplatin-induced nephrotoxicity and improve kidney function in cancer patients.
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Lange, A., W. Witkiewicz, D. Dlubek, L. Maslowski, D. Drabczak-Skrzypek, E. Jaskula, B. Szymczak, D. Duda, and J. Lange. "A Bone Marrow Population Containing Both Hematopoietic and Mesenchymal Stem Cells Constitutively Expressing Genes Pairs For: SDF1-CXCR4, CX3CL-CXCR1 and for VEGF Improves Vascularization When Implanted to Ischemic Legs." Blood 104, no. 11 (November 16, 2004): 4178. http://dx.doi.org/10.1182/blood.v104.11.4178.4178.
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Abstract The BM contains progenitor cells that give rise to hematopoietic tissue and also more primitive mesenchymal stem cells (MSC) which may differentiate into other tissues including endothelial cells. This potential of BM cells has already been employed in clinical studies suggesting that implantation of autologous BM cells may induce angiogenesis in ischemic tissues. In the present study 10 male pts with critical leg ischemia (41–64 yrs) suffering from pain at rest and/or foot ischemic ulceration (9/10 pts) with ABI (ankle/brachial index) <0.5 in 8/10 pts in whom surgical treatments were exhausted were enrolled in this study. 0.5L of BM obtained from the iliac posterior crest were processed in a Cobe Spectra 6.0 separator to remove RBC and to reduce the number of granulocytes. Fresh BM populations and those after processing were evaluated for phenotype characteristics and for the presence of transcripts for VEGF and for SDF1-CXCR4, CX3CL-CXCR1 gene pair expression. Usually 40 ml of cell suspensions were injected in 0.5 ml portions to ischemic muscles and the fate of the pts was evaluated in an out-pts observation setting for 5–7 mths. The number of WBC implanted was (mean±SEM) 30.2x108±4.5 which contained the following percentages of subpopulations CD34+ 1.58±0.25, CD45−CD34− 10.8±0.96, CD45−CD34−CD90+ 0.1±0.02, CD45−CD34−CD105+ 2.8±0.4, CD45−CD34−CD73+ 0.07±0.01 and 24 CFU-F/106 WBC. The positive effect of implantation was seen 2 days after the procedure with substantial pain reduction from 6.17±0.35 to 4.63±1.03 (p=0.04) 10 days and to 3.66±1.35 3 mths after implantation (p=0.034). ABI improved from 0.47±0.07 before to 0.66±0.06 (p=0.02) 10 days and to 0.66±0.07 (p=0.02) 3 mths after. This improvement was followed by ulceration healing in 5/9 pts (area of ulceration prior to implantation was 502.3±269.2 mm2 and 2 mths after was 32.3±23.6 mm2) in 2 pts ulceration healed completely. In 10 cases arteriography performed 3 mths after implantation documented new arteriole formation in 6 pts. The positive effect may not be long lasting in all pts as in 3/10 pts the pain at rest recurred and in 2 pts ulceration progressed 2 mths after implantation. The positive effect of the treatment could not be attributed to any of the described cell populations separately as evaluated by correlation analysis. In this study we identified cells with MSC characteristics in the BM population that were further enriched in MNC and implanted to ischemic muscles. In fresh BM cell populations and those after cell processing, the transcripts for VEGF and SDF1-CXCR4 and CXCL3-CXCR1 pairs were found. Implantation of these cells resulted in early, intermediate and late effects with pain relief, ischemic ulceration healing and finally arteriole length density, respectively. The pace of improvement suggested that the processed BM population while injected to ischemic muscles may act via cyto-/chemokine release with an analgetic effect and local immunity improvement. Furthermore, ulceration healing seen 10 days after implantation followed by neovascularization is likely due to auto/paracrine effects within a population of MSC that express genes facilitating the homing of vascular progenitors and play a role in new vessels formation. Supp by the grant PBZ-KBN-083/P05/2002 from the Polish State Committee Sci. Res.
Dissertations / Theses on the topic "CXCL12/CXCR4 axi"
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BIONDI, MARTA. "Enhancing AML CAR CIK therapeutic potency increasing the localization of engineered cells in the malignant niche and its selectivity by LSCs specific targeting." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2022. http://hdl.handle.net/10281/365153.
Full textAbstract:
La terapia CAR-T rappresenta un approccio promettente, ma ha riportato una ridotta efficacia nella leucemia mieloide acuta (AML), a causa dell’eterogeneità del tumore, dell’assenza di antigeni target AML-specifici e del ruolo del microambiente leucemico nella protezione dei blasti e delle cellule staminali leucemiche (LSC). La nicchia midollare, nella quale risiedono le LSC, è coinvolta in attività che promuovono la progressione leucemica e sopprimono l’ematopoiesi sana. Quindi ipotizziamo che bersagliare le LSC nascoste nella nicchia potesse migliorare l’efficacia delle CAR-T. Per testare la nostra ipotesi, abbiamo agito su due fronti: 1) promuovere una migrazione efficiente delle CAR-T nella nicchia midollare, 2) selezionare un antigene target ristretto ai blasti leucemici e alle LSC. Prima, abbiamo proposto una strategia per guidare le cellule CD33.CAR CIK (Cytokine-Induced Killer), una sottopopolazione di cellule T effettrici, verso la nicchia leucemica. La chemochina CXCL12, rilasciata dalle cellule mesenchimali stromali (MSC), nella nicchia midollare, e il suo recettore CXCR4, sono coinvolti nella regolazione della migrazione dei leucociti all’interno della nicchia. Quindi, abbiamo ipotizzato che sfruttare questo asse potesse migliorare la capacità di homing delle CD33.CAR-CIK nella nicchia e favorire l’eradicazione della leucemia. Tuttavia i protocolli di manipolazione ex vivo delle CD33.CAR-CIK riducono l’espressione di CXCR4, compromettendo la capacità delle cellule infuse di raggiungere la nicchia. Quindi per implementare la capacità di homing delle CD33.CAR-CIK nel microambiente midollare, abbiamo sviluppato delle CD33.CAR-CIK overesprimenti CXCR4, nella sua forma wild-type o iperattiva mutata. Le CIK ingegnerizzate con i costrutti CD33.CAR-CXCR4 hanno mostrato un consistente aumento dell’espressione di CXCR4, senza riportare alterazioni fenotipiche e nelle funzioni effettrici CAR-associate. Inoltre, rispetto alle CD33.CAR-CIK, le cellule CD33.CAR-CXCR4WT -CIK ed in particolare le CD33.CAR-CXCR4MUT-CIK hanno dimostrato non solo una superiore risposta chemotattica in vitro verso il CXCL12 ed i surnatanti delle MSC, ma anche un aumentato homing in vivo. In seguito, per promuovere lo sviluppo di un approccio CAR-T più efficace e sicuro, abbiamo proposto di re-indirizzare il CAR verso un antigene espresso selettivamente dalle cellule AML, ma assente sulle cellule staminali ematopoietiche (HSC). TIM-3 è un immune checkpoint, svolge un ruolo centrale nella regolazione delle risposte immunitarie nell’AML e costituisce un marcatore selettivo per le LSC, senza essere espresso dalle HSC. Abbiamo disegnato un CAR di terza generazione diretto contro TIM-3, utilizzando la porzione scFv derivante da un anticorpo monoclonale anti-TIM-3. In vitro, le TIM-3.CAR-CIK hanno dimostrato di eliminare sia le linee AML che i blasti primari, senza dare tossicità verso le cellule TIM-3+ sane, come le CIK attivate, i monociti e le cellule NK. Inoltre, le TIM-3.CAR-CIK hanno eliminato in maniera selettiva le LSC (CD34+ CD38-). Infine, le TIM-3.CAR-CIK hanno mantenuto le loro capacità effettrici nonostante multiple ristimolazioni in vitro, gettando le basi per lo studio di questo costrutto in vivo. Complessivamente, entrambi gli approcci, uno implementando l’homing delle CAR-CIK alla nicchia midollare e l’altro conferendo una superiore selettività, potrebbero migliorare l’efficacia della terapia CAR-T nel contesto dell’AML.Chimeric Antigen Receptor (CAR) T-cell therapy has produced remarkable clinical responses in patients affected by acute lymphoblastic leukemia. Unfortunately, CAR T-cells have not been equally successful in acute myeloid leukemia (AML) due to tumor heterogeneity, lack of truly AML-restricted target antigens and the role of leukemia microenvironment in blasts protection and leukemia stem cells (LSCs) maintenance. Specifically, the bone marrow (BM) niche, where LSCs reside, is involved in leukemia promoting activities whilst suppressing normal hematopoiesis. Therefore, we hypothesized that targeting LSCs at their location may enhance the potency and selectivity of CAR-T cells. To address this issue, we have designed two aims: 1) promote rapid and efficient localization of CAR T-cells within the BM niche, 2) select a leukemia-restricted antigen to specifically target AML blasts and LSCs. First, we proposed to harness CD33.CAR-redirected Cytokine-Induced Killer (CIK) cells, an alternative effector T-cell population with acquired NK-like cytotoxic activity as well as minimal alloreactivity, to selectively route their activity to leukemia transformed niche. The chemokine ligand 12 (CXCL12), released by mesenchymal stromal cells (MSCs) within the medullary niche, and its chemokine receptor 4 (CXCR4) are two pivotal players regulating leukocytes trafficking to the BM. In AML, CXCL12 interacts with CXCR4 overexpressed on blasts, promoting their migration and homing in the niche. Hence, taking advantage of this axis might facilitate CD33.CAR-CIK cells homing to the BM and therefore leukemia eradication. However, ex vivo manipulation protocols of CD33.CAR-CIK cells consistently downregulate CXCR4 expression and may affect the capacity of adoptively infused cells to migrate to BM and exert their anti-leukemic action. Therefore, to improve CD33.CAR-CIKs homing in the BM microenvironment we have developed CD33.CAR-CIK cells overexpressing CXCR4, in its wild-type or hyperactive mutant form. Notably, CIK cells engineering with CD33.CAR-CXCR4 constructs led to a consistent increase in CXCR4 expression, without altering CIK cells phenotype and CAR-related effector functions. Interestingly, compared to conventional CD33.CAR-CIK cells, CD33.CAR-CXCR4WT and especially CD33.CAR-CXCR4MUT-CIK cells demonstrated significantly superior in vitro chemotactic response toward CXCL12 and MSC-derived supernatants, and greater in vivo BM homing ability and persistence. Furthermore, to develop an effective anti-AML CAR T-cell therapy, it is fundamental to identify a LSC-specific marker, sparing the normal counterpart of hematopoietic stem cells (HSCs). T-cell immunoglobulin and mucin protein 3 (TIM-3) is an immune checkpoint molecule, it plays a central role in immune responses in AML and it is an LSC-specific marker, lacking expression on HSCs. Therefore, we designed a third-generation anti-TIM-3.CAR using the single-chain fragment variable (scFv) derived from an antagonistic ligand-blocking anti-TIM-3 antibody. In vitro, TIM-3.CAR-CIK cells efficiently killed both AML cell lines and primary AML blasts, but not normal TIM-3+ activated CIK cells, monocytes and NK-cells. Notably, we observed selective elimination of primary LSC-enriched population (CD34+ CD38-). Furthermore, TIM-3.CAR-CIK cells maintained their effector functions despite multiple in vitro restimulations, setting the basis for further exploration in in vivo models. Overall, both approaches, one improving CAR-CIK cells homing to the transformed niche and the other conferring superior safety and selectivity, might improve the efficacy of anti-AML CAR-CIK therapy.
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SOLARI, AGNESE. "CXCR4/CXCR7-CXCL11/CXCL12 AXIS PROMOTES MALIGNANT PHENOTYPE IN PUTATIVE STEM CELLS FROM HUMAN MENINGIOMAS." Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/946169.
Full textAbstract:
Meningioma is the most frequent primary tumor of the central nervous system. The
greatest percentage of meningiomas is benign tumors (WHO grade I). However,
although surgical and radiotherapy techniques have significantly improved over the
years, some meningiomas, independently from the grading, are refractory to
multimodality therapies, and recur and/or undergo malignant transformation,
representing an unsolved therapeutic challenge. Therefore, beside histopathologic
benign appearance, biologically aggressive meningiomas need to be molecularly
characterized, to identify novel therapeutic targets.
In malignant tumors, recurrence is mainly ascribed to the presence of cancer stem
cells (CSCs) which are expression of tumor cell heterogeneity, and sustain
tumorigenesis, metastasization and drug resistance.
CSCs are characterized by stem cell marker expression, self-renewal, and ability to
differentiate into tumor-specific cell types. Recently, CSCs and their functional role
have been also studied in benign tumors, including meningioma. A range of genes
and proteins have been proposed to identify meningioma stem-like cells, among
them CD105, a transmembrane glycoprotein, involved in angiogenesis and in the
progression of a variety of tumors. Stemness, as well as cancer cell aggressive
behavior, is a cell property strictly linked to tumor microenvironment: reciprocal
interactions between growth factors, cytokines and chemokines released by both
CSCs and other cell types forming the niche, modulate each other to sustain tumor
growth. Chemokine signaling, and the CXCL11/CXCL12-CXCR4/CXCR7 system in
particular, drives cell proliferation and migration in several solid tumors. On these
premises, this study is focused on the isolation and characterization of stem-like
cells from post-surgical samples of human meningiomas, delving deeply into the
role of this subpopulation in meningioma aggressive behavior. Moreover, we
analyzed the contribution of CXCR4-7 receptors in the regulation of their biological
properties. Twenty-eight primary cell cultures have been obtained from 35
meningiomas, and maintained in stem cell-permissive culture conditions to enrich
in CSCs. Putative meningioma stem cells rapidly grow, form meningospheres and
express stem markers, such as Sox2, NANOG, CD133 and Oct-4. Conversely, CD105
was not differentially expressed between stem-like cells and their “non-stem”
counterpart, cells grown in serum-containing medium. Moreover, stem-like cells
displayed high migratory capacity and in vitro angiogenic activity, supporting their
malignant phenotype. Meningioma stem-like cells displayed a distinct chemokinereceptor
profile from “non-stem” cell population, and selectively respond to in vitro
CXCL11 and CXCL12 stimulation enhancing proliferation, migration and vascular
mimicry. Pharmacological inhibition of individual CXCR4 or CXCR7 significantly
impaired CXCL12- and CXCL11-induced proliferation, chemotaxis and vessel-like
structure formation, therefore suggesting that these activities are mediated by both
receptors. We speculated that these receptors act as heterodimers, formed upon
ligand activation and that the blockade of one of them results in a complete
inhibition of biological effects.
Overall our results, collected from a large number of meningioma cell cultures
derived from different patients, allow the identification of a tumor subpopulation
endowed with comm
on stem cell-like features, and suggest that both CXCR4 and
CXCR7 signaling sustains meningioma stem cell phenotype. Prospectively, the
isolation and culture of stem-like cells directly from the meningioma tissues will
allow to test new therapeutic compounds to block meningioma growth and
invasiveness, in particular for those tumors showing an unpredictable aggressive
behavior. In this context, we propose that the CXCR4-7 chemokinergic system might
represent a relevant pharmacological target.
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Mikami, Sakae. "Blockade of CXCL12/CXCR4 axis ameliorates murine experimental colitis." Kyoto University, 2009. http://hdl.handle.net/2433/124258.
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Ogawa, Ryotaro. "Loss of SMAD4 Promotes Colorectal Cancer Progression by Recruiting Tumor-Associated Neutrophils via the CXCL1/8-CXCR2 Axis." Kyoto University, 2019. http://hdl.handle.net/2433/245315.
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Goh, Poh. "Roles of protein kinase C and arrestin in migration of cells via CXCR4/CXCL12 signalling axis." Thesis, University of East Anglia, 2018. https://ueaeprints.uea.ac.uk/67806/.
Full textAbstract:
Aim: The chemokine system not only coordinates leukocyte migration in immunity and inflammation, but it is also implicated in the pathogenesis of many human diseases, including cancer. The expression of chemokines and their receptors is altered in many malignancies and leads to aberrant chemokine receptor signalling. Emerging evidence indicates that the tumour microenvironment has critical roles in all aspects of cancer biology, including growth, angiogenesis, metastasis and progression. One of the important representatives of this system are the chemokine ligand CXCL12 and its receptor, CXCR4 as they are most commonly found on human and murine cancer cells. Our aims are to study and understand if there are any differences in activation of signalling molecules in the downstream signalling cascades in CXC- chemokine receptors in different cell types, and to identify the importance of different effector proteins in migration of cells; the two proteins of interest include Protein Kinase C (PKC) and arrestins. Methodology: Experimentation was undertaken in MCF-7 breast cancer cells and Jurkat leukemic T-lymphocytes which both naturally express the chemokine receptor CXCR4. Small molecule inhibition and protein overexpression was used in chemotaxis and calcium release assays to measure cellular responses. Immunocytochemistry was used to determine the effect of protein blocking and protein overexpression on receptor internalisation, protein localisation and the formation of cellular structures associated with migration. Results: Inhibition of PKC has no effect on Jurkat cell migration, but it blocks MCF-7 cell migration showing that there is a difference in the usage of PKC in different cell types. Arrestin 3 is important for migration in both suspension Jurkat cells and adherent breast cancer MCF-7 cells. Conclusion: Our study shows that CXCL12-induced migration may be arrestin 3 mediated. We have also shown that activation of signalling molecules needed for CXCL12-induced migration can differ between different cell lines. Overall, the research in this thesis has identified potential signalling molecules that can be targeted to interfere with migration of cells.
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Chow, Yan Ching Ken. "Role and Molecular Basis of the CXCL12-signalling Axis in the Pathogenesis of WHIM syndrome and the carcinogenesis associated with human papillomavirus (HPV) infection." Paris 7, 2008. http://www.theses.fr/2008PA077129.
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Le syndrome WHIM (SW) est un déficit rare caractérisé par une leuco-neutropénie (e. X. Myélokathexis) et la profusion des verrues cutanées et de carcinomes ano-génitaux due au Papillomavirus Humain (HPV). Il est associé à des dysfonctions du chimiorécepteur CXCR4 en réponse à son ligand SDF-1/CXCL12, qui sont souvent liées à des mutations hétérozygotes de CXCR4 conduisant à la troncation de l'extrémité C-terminale du récepteur impliquée dans le recrutement de l'arrestine (βarr) pour le processus de désensibilisation. Le récepteur muté (e. X. CXCR4¹º¹³) qui n'est donc plus désensibilisé et présente un gain de fonction confère aux leucocytes des patients des réponses exacerbées à CXCL12 dont nous proposons qu'elles contribuent à la pathogenèse du SW. Dans cette thèse, nous montrons que ces dysfonctions impliquent une association inattendue entre CXCR4¹º¹³ et βarr2. Cette interaction se traduit par une activation accrue et prolongée des voies de signalisation dépendantes de βarr2 en aval du récepteur et également de l' intégrité de la troisième boucle intracellulaire de CXCR4¹º¹³. Nous identifions que CXCR4¹º¹³ forme des dimères avec son homologue sauvage au sein desquels une association possible renforcée entre barr2 et CXCR4¹º¹³ pourrait contribuer aux réponses exacerbées à CXCL12. L'expression anormale de CXCL12 que nous avions identifiée dans les lésions dues à HPV provenant d'individus souffrants ou non du SW et le rôle critique de cette chimiokine dans le développement de nombreux cancers suggèrent l'implication de cet axe de signalisation dans la pathogénie virale. Dans les kératinocytes immortalisés par HPV à haut-risque, nous observons une expression anormale de CXCL12 et de ses deux récepteurs que nous caractérisons comme étant dépendante des protéines virales HPV-E6/7 et nécessaire à la prolifération et la migration des kératinocytes. Dans le contexte du SW, ce processus en coopération avec l'activation incontrôlée de CXCR4¹º¹³ pourrait contribuer à la maîignisation des lésions ano-génitales alors même que nous y avons identifié la seule présence d'HPV à faible potentiel cancérogène (bas-risque)The WHIM syndrome (WS) is a rare immunodeficiency characterised by severe leukoneutropenia (e. G. Myelokathexis) and profuse human papillomavirus (HPV)-associated skin lesions and malignant ano-genital cohdyloma. The disease links to dysfunctions of the CXCR4 chemokine receptor in response to its ligand SDF-1/CXCL12, and associates in many cases to heterozygous mutations causing truncation in the cytoplasmic tail of the receptor that is important for the β-arrestin (βarr)-mediated receptor desensitisation process. Such truncated receptor (e. G. CXCR4¹º¹³) displays no desensitisation and thus manifests a gain of function in response to CXCL12 in leukocytes derived from WS patients, which likely contribute to the pathogenesis of the disorder. In this study, we demonstrated that such dysfunctions are in fact dependent on an unexpected interaction between βarr2 and CXCR4¹º¹³. Upon CXCL12 stimulation, the CXCR4¹º¹³receptor displays an augmented and prolonged |3arr2-dépendent signalling that relies on the integrity of the third intracellular loop of the receptor. We have also observed the existence of CXCR4wt/CXCR4¹º¹³ heterodimer from which the possible enhanced parr2/CXCR4¹º¹³ interaction may contribute to the augmented response of the receptor to CXCL12. With the abnormal expression of CXCL12 we observed in HPV-induced lesions derived from both WS and non-WS patients, and the critical role of the chemokine in tumor growth and metastasis, we speculate on the existence of an HPV/CXCL12 interplay that could be crucial for the viral-mediated pathogenesis. Using keratinocytes immortalised by the subgenomic fragment of high-risk HPV, we showed an HPV-E6/7-dependent expression of CXCL12 and its receptors and the critical role of this signalling axis in the prolifération and motility of these cells. In WS, such HPV/CXCL12-interplay may synergise with the hyperfunctioning of CXCR4, and contribute to the malignant development of ano-genital condyloma that is unusually associated with low-risk HPV - the only viral subtype we identified in these lesions
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Swidenbank, Isabella. "The role of the CXCR4-CXCL12 chemokine axis in melanoma metastasis to the normal and fibrotic liver." Thesis, University of Newcastle upon Tyne, 2014. http://hdl.handle.net/10443/2612.
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Malignant melanoma represents the most aggressive form of skin cancer. Although early stage disease is treatable through surgical excision alone, late stage tumours frequently metastasise to the liver, at which point treatment options remain limited. Migration of melanoma towards metastatic sites has been shown to be associated with the CXCR4-CXCL12 chemokine axis. The chemokine receptor CXCR4 is expressed by melanoma cells and the chemokine CXCL12 is secreted by the liver. Expression of CXCL12 has been shown to be increased in liver fibrosis and therefore it was hypothesized that cells involved in liver damage may promote melanoma metastasis to this organ. CXCR4 and CXCL12 expression in melanoma and liver cells in vitro and in vivo was examined by RT-PCR, Western blotting and immunohistochemical staining. Chemotaxis assays were performed to test the ability of AMD11070 to inhibit migration of melanoma cells. Quantitative RT-PCR and Western blotting determined the influence of different fibrosis models (Carbon tetrachloride (CCl4), Bile Duct Ligation (BDL) and Methapyrilene (MP)) on CXCL12 expression. Furthermore, the migration of melanoma was examined in animal models of liver injury. Results showed that melanoma cells and different liver cell types (myofibroblasts and biliary epithelial cells) express both CXCR4 and CXCL12. CXCR4 expression in melanoma promoted migration of tumour cells towards CXCL12 secreting liver cells and AMD11070 inhibited this. CXCR4 and CXCL12 proteins of varying sizes were observed in vivo suggesting that post translational modifications of these proteins may occur. CXCL12 expression increased in three models of chronic liver injury; CCl₄, BDL and MP. In an animal model, murine melanoma cells metastasized to the lungs and to both the fibrotic and normal liver. These findings suggest that the reduction of liver cells secreting CXCL12 may help to reduce melanoma metastasis to this organ.
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Rondeau, Vincent. "Rôle de la désensibilisation de CXCR4 dans la spécification lympho-myéloïde des progéniteurs hématopoïétiques multipotents. Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization New method to obtain lymphoid progenitors CXCR4-driven mitochondrial metabolic pathways shape the lympho-myeloid fate of hematopoietic multipotent progenitors." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ022.
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Les cellules souches et progéniteurs hématopoïétiques (CSPHs), incluant les progéniteurs multipotents (MPPs), sont responsables de la production des cellules immunes circulantes. Ils résident dans la moelle osseuse (MO) au sein de structures spécialisées, les niches endostéale et (péri)-vasculaire, qui régulent la spécification et l'engagement lymphoïde versus myéloïde des CSPHs. Dans la MO, le couple formé par la chimiokine CXCL12 et l’un de ses récepteurs, CXCR4, exerce un rôle clé dans la régulation de la rétention et la quiescence des CSPHs. Ces processus sont dérégulés dans le Syndrome WHIM (SW), une maladie immuno-hématologique rare liée à des mutations autosomiques dominantes du gène codant CXCR4, qui altèrent la désensibilisation du récepteur et conduisent à un gain de fonction en réponse à CXCL12. Cliniquement, le SW se caractérise notamment par une profonde leucopénie circulante qui affecte les lignages lymphoïde et myéloïde et dont les mécanismes restent à déterminer. Grâce à un modèle murin génétiquement modifié du SW et à l'accès à des prélèvements biologiques de patients atteints du SW, nous avons testé l'hypothèse que la lymphopénie circulante associée au SW résultait de défauts hématopoïétiques dans la MO. Nous avons révélé un rôle clé de la désensibilisation de CXCR4 dans la différenciation lymphoïde des CSPHs et identifié les MPPs comme étant le stade défectueux dans le SW. La divergence entre les lignages lymphoïde et myeloïde se produit précisément à ce stade au sein duquel règne une hétérogénéité : les MPP2/3 sont biaisés myéloïde et les MPP4 sont orientés lymphoïde. Notre compréhension de la façon dont les signaux extrinsèques (niches) et intrinsèques aux MPPs déterminent leur devenir lymphoïde versus myéloïde est encore parcellaire. Dans ce contexte, l’objectif de ma thèse a été de déterminer si et comment la signalisation de CXCR4 régule la dépendance énergétique des MPPs et à comprendre comment les voies métaboliques façonnent leur spécification lympho-myéloïde. Dans la MO des souris porteuses de la mutation gain de fonction de Cxcr4, nous avons observé une diminution du nombre de MPP4 qui contrastait avec l'augmentation des MPP2/3. L’analyse de prélèvements médullaires de patients a également permis de rapporter une diminution de la fréquence des progéniteurs lymphoïdes et une augmentation de celle des progéniteurs myéloïdes. Chez la souris mutantes, ce biais myéloïde du compartiment de MPPs s'avèrait associé à une expansion anormale et une reprogrammation moléculaire et métabolique des MPP4. Fait marquant, un traitement chronique par l’AMD3100, un antagoniste de CXCR4, permettait de normaliser le nombre de MPP4 dans la MO, de restaurer leurs propriétés métaboliques, et de corriger la lymphopénie des souris mutantes. Par conséquent, nos résultats suggèrent que l’axe CXCL12/CXCR4 est requis au maintien du potentiel lymphoïde des MPP4 au travers de la modulation de leur activité métabolique mitochondrialeHematopoietic stem and progenitor cells (HSPCs), including the multipotent progenitors (MPPs), are responsible for replenishing immune cells. They reside in bone marrow (BM) endosteal and (peri)-vascular niches, which provide all cellular and molecular components required for their lifelong maintenance and fate. Among them, the CXCL12 chemokine and one of its receptor, CXCR4, exert a dominant role in promoting HSPC retention and quiescence. These processes are deregulated in the WHIM Syndrome (WS), a rare immunodeficiency caused by inherited heterozygous autosomal gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor. Clinically, WS is notably characterized by severe, chronic circulating lymphopenia whose mechanisms remain to be elucidated. Using a mouse model carrying a naturally occurring WS-linked Cxcr4 mutation as well as human BM and blood samples, we explored the possibility that the lymphopenia in WS originates from defects at the HSPC level in BM. We reported that Cxcr4 desensitization is required for lymphoid differentiation of HSPCs and further identified the MPP stage as defective in mutant mice. The divergence between lymphoid and myeloid lineages occurs at the MPP stage, which is composed of distinct subpopulations, i.e., MPP2 and MPP3 are reported as distinct myeloid-biased MPP subsets that operate together with lymphoid-primed MPP4 to control blood leukocyte production. Our understanding of how cell-extrinsic niche-related and cell-intrinsic cues drive the lymphoid versus myeloid fate decision of MPPs is still fragmentary. Therefore, my PhD project aimed at determining whether and how CXCR4 signaling regulates bioenergetics demands of MPPs and at understanding how these metabolic pathways shape the lympho-myeloid fate of MPPs. We unraveled a myeloid skewing of the HSPC compartment in BM of WS mice and patients. In mutant mice, this partly relied on the contraction of the MPP4 pool and on cell-autonomous molecular and metabolic changes that reprogramed MPP4 away from lymphoid differentiation. Interestingly, chronic treatment with the CXCR4 antagonist AMD3100 normalized mitochondrial metabolism and fate of MPP4, while correcting circulating lymphopenia in WS mice. This study provides evidence that CXCR4 signaling acts as an essential gatekeeper for integrity of the mitochondrial machinery, which in turn controls lymphoid potential of MPP4
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Li, Yin [Verfasser], Andreas [Akademischer Betreuer] Knopf, Murat [Gutachter] Bas, and Andreas [Gutachter] Knopf. "CXCR4-CXCL12 axis in head and neck squamous cell carcinoma regarding HPV status / Yin Li ; Gutachter: Murat Bas, Andreas Knopf ; Betreuer: Andreas Knopf." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1236343069/34.
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Patil, Ashwini [Verfasser], and Joachim [Akademischer Betreuer] Göthert. "The CXCL10/CXCR3 axis cross-talk between emerging T cell acute lymphoblastic leukemia and thymic epithelial cells / Ashwini Patil ; Betreuer: Joachim Göthert." Duisburg, 2021. http://d-nb.info/1225294649/34.
Full textConference papers on the topic "CXCL12/CXCR4 axi"
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Costello, Christine M., Brian McCullagh, Katherine Howell, John A. Belperio, Michael P. Keane, Sean P. Gaine, and Paul McLoughlin. "A Role For The CXCL12/CXCR7/CXCR4 Axis In Pulmonary Hypertension." In American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3399.
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Clements, D., LM Markwick, and SR Johnson. "The CXCR4/CXCL12 Axis in Lymphangioleiomyomatosis." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4350.
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Yu, Minghuan, and Mary A. Kosir. "Abstract 5276: CXCL7/CXCR2 axis and invasion." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5276.
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Balthazar, L., M. Cebo, J. Rheinlaender, D. Rath, M. Gawaz, T. E. Schäffer, M. Lämmerhofer, and M. Chatterjee. "Platelet Lipidome and Lipid Induced Thromboinflammatory Actions are Influenced by the CXCL12-CXCR4-CXCR7 Axis." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680094.
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Balthazar, L., M. Cebo, J. Rheinlaender, D. Rath, M. Gawaz, T. E. Schäffer, M. Lämmerhofer, and M. Chatterjee. "Platelet Lipidome and Lipid Induced Thromboinflammatory Actions are Influenced by the CXCL12-CXCR4-CXCR7 Axis." In 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-1680195.
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D'Alterio, Crescenzo, Antonio Avallone, Paolo Delrio, Fabiana Tatangelo, Biagio Pecori, Elena Di Gennaro, Rosario Vincenzo Iaffaioli, Paolo Muto, Gerardo Botti, and Stefania Scala. "Abstract 1145: CXCR4-CXCL12-CXCR7 axis predicts prognosis in locally advanced-Chemo Radiotherapy (CRT) treated rectal cancer patients." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1145.
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Singh, Seema, Sudha Talwar, Sanjeev Srivastava, Sarah Braune, Laurie B. Owen, and Ajay P. Singh. "Abstract 5378: Targeting CXCL12/CXCR4 signaling axis for pancreatic cancer therapy." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5378.
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Mei, Junjie, Yuhong Liu, Ning Dai, Kristin M. Hudock, Susan H. Guttentag, Jay K. Kolls, G. Scott Worthen, and Paula M. Oliver. "CXCR2 And CXCL5 Regulate IL-17/G-CSF Axis And Neutrophil Homeostasis." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1067.
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Riveiro, Maria E., Maria Serova, Safi Dokmak, Ivan Bieche, Sebastien Albert, Caroline Halini, Eric Raymond, and Sandrine Faivre. "Abstract 4264: CXCL12-CXCR4 axis in sunitinib-sensitive and -resistant hepatocarcinoma cells." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4264.
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Zhilin-Roth, Alisa, and Jill A. Macoska. "Abstract 2021: The CXCL12/CXCR4 axis drives epithelial-mesenchymal transition in renal cell carcinoma." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2021.
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