title: Blockade of IL-7Rα alleviates collagen-induced arthritis via inhibiting Th1 cell differentiation and CD4+T cell migration.
abstract: T cell response is crucial to the pathogenesis and progression of rheumatoid arthritis (RA). IL-7/IL-7R axis has significant effect on CD4+T cell response, including proliferation, differentiation, survival and migration. However, whether blockade of IL-7/IL-7R axis signaling can relieve RA and what is the potential treatment mechanisms are still remaining unclear. In this paper, we established collagen-induced arthritis (CIA) model and observed the effect of IL-7Rα antibody in the treatment of CIA mice. It is demonstrated that IL-7Rα antibody significantly alleviated clinical symptoms of CIA mice, accompanied with reduced CD4+T cell number in both spleen and joints. Decreased CII-specific CD4+T cell proliferation and reduced mRNA expression of inflammatory cytokines in IL-7Rα antibody-treated mice were observed. Subsequently, IL-7Rα antibody treatment in vivo downregulated the percentages of Th1 and Th17 cells and the mRNA expression of T-bet and RORγt gene. Moreover, it was found that IL-7 promoted Th1 cell differentiation in vitro, while having no effect on Th17 cell differentiation. In addition, administration of IL-7Rα antibody reduced the mRNA expression of chemokine receptors (CCR7, CXCR3, CXCR6 and XCR1) on CD4+T cells and chemokine CXCL2 in joints. The results suggested that IL-7Rα antibody treated CIA mice via the inhibition of CII-specific CD4+T cell proliferation, the reduction of Th1 cell differentiation and the restrain of CD4+T cell migration to joint lesion site. This investigation indicates that IL-7Rα is a potential therapeutic target for RA.
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Department of Allergy and Immunology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Guojue
authors.initials: G
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address: hnie0823@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D060888:Real-Time Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D055114:X-Ray Microtomography
chemical_list: D000906:Antibodies; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain
keywords: CD4(+) T cells; CIA; IL-7; IL-7Rα antibody