The role of Syndecan-4 in the development of rheumatoid arthritis (54.23)

Abstract

Abstract Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan has been implicated as a critical mediator for inflammatory responses. Recent report has demonstrated that dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand (DC-HIL) binds to Syn4 on activated T cells, resulting in the inhibition of T cell responses. Here, we have investigated the role of Syn4 in the development of Rheumatoid Arthritis (RA). We have used two RA models; T cell-dependent collagen-induced arthritis (CIA) model and T cell-independent collagen antibodies-induced arthritis (CAIA) model. In CAIA model, Syn4-wild-type and Syn4-deficient (Syn4 KO) mice showed similar levels of clinical severity. In contrast, in CIA model, Syn4 KO mice revealed attenuated RA development. Syn4 expression was detectable on activated CD4+ T cells and B cells in the draining LN (dLN). Syn4 KO mice showed a tendency to generate reduced numbers of Th1 and Th17 cells in the dLN after immunization, and helper T cells generated in Syn4 KO mice revealed different expression patterns of chemokine receptors. Although both groups showed comparable numbers of Tfh and GC (germinal center) B cells, Syn4 KO mice produced lower level of type-II collagen-specific antibody, as compared with WT mice. These results suggest that Syn4 may regulate the development of RA by modulating T and B cell responses. We are currently investigating if Syn4-deficiency affects the functions of Tfh and GC B cells.