A novel B7 family member, B7-H3 is preferentially expressed on the cell surface of synovial monocytes in rheumatoid arthritis (RA) (BA7P.153)

Abstract

Abstract B7-H3, a newly identified B7 family member, has functional duality as a T-cell costimulator and coinhibitor that fine-tunes T-cell mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Monocytes also play crucial roles in the pathophysiology of various autoimmune diseases. However, the immunological role of B7-H3 in RA has not been defined. We aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments provide evidence that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, the expression level of 4Ig B7-H3 on synovial monocytes inversely correlates with clinical parameters such as CRP levels, ESR, and DAS28. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles thereby affecting the pathogenesis of RA.