Because dendritic cells (DCs) play critical roles in the pathogenesis of
rheumatoid arthritis, modulation of their functions could serve as a novel
therapy. In this study, we demonstrated that
FTY720 treatment significantly suppressed the incidence and severity of
collagen-induced arthritis (CIA) in DBA/1J mice via the modulation of DC functions. In FTY720-treated CIA mice, a decrease in the number of DCs in local draining lymph nodes (LNs) was observed. In vitro,
FTY720 inhibited the trafficking of LPS-stimulated bone marrow-derived DCs (BMDCs). Decreased secretion of CCL19 and downregulation of CCR7 on DCs may explain the mechanisms underlying the impairment of DC migration induced by
FTY720. In a DC-induced mouse
arthritis model,
FTY720 treatment also suppressed the incidence and severity of
arthritis, which was correlated with a decrease in the migration of injected BMDCs to draining LNs. Although lower levels of costimulatory molecules (CD40, CD80, and CD86) and I-A(q) expressed on LN DCs were observed in FTY720-treated mice, in vitro analysis showed no effect of
FTY720 on LPS-stimulated BMDC maturation. Furthermore, LN cells from FTY720-treated CIA mice displayed diminished production of proinflammatory
cytokines in response to
collagen II and Con A stimulation. In addition, the ratio of Th1/Th2 in the draining LNs of mice with DC-induced
arthritis was decreased upon
FTY720 treatment. This finding was consistent with the fact that
FTY720 suppressed IL-12p70 production in cultured BMDCs. Taken together, these results indicate that inhibition of DC migration by
FTY720 may provide a novel approach in treating
autoimmune diseases such as
rheumatoid arthritis.