The role of syndecan-4 in the development of rheumatoid arthritis (P4052)

Abstract

Abstract Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan (HSPGs) expressed by several types of cells, has been implicated as a critical mediator for inflammatory responses. Recent report suggested that HSPGs including Syn4 expressed by B lymphocytes regulate B cell development and survival. Here, we have investigated the role of Syn4 in the development of murine models of Rheumatoid Arthritis. In type-II collagen-induced arthritis (CIA) model, which is both T and B cell-dependent model, we found that Syn4-deficiency showed attenuated clinical severity and pathological features, although Syn4-deficient (Syn4-KO) mice generated unimpaired numbers of Th1 and Th17 cells in the draining inguinal LN (dLN). Because Syn4 expression was highly detectable on B cells, we analyzed type-II collagen-specific antibody (Ab) production, and found that Syn4-KO mice generated comparable levels of IgM, but significantly reduced levels of total IgG, IgG2a and IgG2b compared with WT mice. Reduction of collagen-specific IgG Abs in Syn4-KO mice was also evident by defective formation of germinal center (GC) in the dLN. In addition, we found that Syn4-KO mice showed reduced numbers of B cell subsets (total B cells, follicular B cells and GC B cells) in the dLN following immunization, although the numbers of follicular helper T cells were comparable between both groups. These results suggest that Syn4 modulates CIA development through enhancing the generation of GC formation and Ab production.