Interleukin-21 signaling in B cells, but not in T cells, is indispensable for the development of collagen-induced arthritis in mice. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Sakuraba, Koji; Oyamada, Akiko; Fujimura, Kenjiro; Spolski, Rosanne; Iwamoto, Yukihide; Leonard, Warren; Yoshikai, Yasunobu; Yamada, Hisakata
• Is Part Of: Arthritis research & therapy. Volume 18:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Interleukin-21 -- Collagen-induced arthritis -- Rheumatoid arthritis -- Cytokine -- B cell; Arthritis -- Periodicals; Arthritis -- Treatment -- Periodicals; 616.722005
• DOI: 10.1186/s13075-016-1086-y
• Languages: English
• ISSNs: 1478-6362

Abstract

Abstract Background Interleukin-21 (IL-21) is a T-cell-derived cytokine whose receptor is expressed on a variety of cells and therefore might have pleiotropic roles in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the involvement of IL-21 signaling in the development of collagen-induced arthritis (CIA), an animal model of RA, using IL-21 receptor knockout (Il21r KO) mice. Methods Il21r KO mice or wild-type (WT) C57BL/6 mice were immunized with chicken type II collagen (CII) emulsified in complete Freund adjuvant on day 0 and were given a boost injection on day 21. The production of anti-CII antibody, development of T-cell and B-cell subsets, and T-cell responses to CII were analyzed. CIA was induced inRag2 KO mice to which combinations of WT orIl21r KO CD4 T cells and WT orIl21r KO B cells had been transferred, in order to examine the role of IL-21 signaling in each cell subset. Results Il21r KO mice were resistant to the development of CIA. CII-specific IgG but not IgM production was impaired inIl21r KO mice. This is consistent with a reduction of germinal center B cells in the draining lymph nodes. In contrast, CII-specific Th1 and Th17 responses were unaffected inIl21r KO mice. There was also no difference in the number of CII-specific follicular helper T cells between WT andIl21r KO mice. By analyzing the development of CIA in T-cell and B-cell mixed transfer experiments, we confirmed that IL-21 receptor expression on B cells, but not on T cells, was essential for the development of CIA. Conclusion IL-21 signaling in B cells, but not in T cells, plays essential roles in the production of pathogenic autoantibodies that induce CIA development.