Rheumatoid arthritis (RA) is a chronic inflammatory
autoimmune disease distinguished by synovial
hyperplasia and a progressive destruction of joints. T cells are critical players in the pathogenesis of RA. We have previously identified a novel
immune checkpoint molecule, TAPBPL, that inhibits T cell functions in vitro. As a model for human RA, we investigated the ability of the TAPBPL
protein to ameliorate
collagen type II (CII)-induced
arthritis (CIA) in mice that were injected with recombinant TAPBPL or a control
protein. The mice were analyzed for CIA development, immune cells, and their responses. We found that TAPBPL
protein significantly decreased CIA incidence and reduced clinical and pathological
arthritis scores, which were related to a lower number of activated CD4 T cells but a greater number of regulatory T cells (Tregs) in the spleen, and a reduction of Th1/Th17 inflammatory
cytokines in the joints and serum. Importantly, TAPBPL
protein inhibited CII-specific T cell growth and Th1 and Th17
cytokine expression and reduced the production of CII
autoantibodies in the serum. Our results suggest that TAPBPL
protein can ameliorate CIA in mice and has the potential to be used in the treatment of patients with RA.