Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production

Summary Oxidative stress is involved in the pathophysiology of rheumatoid arthritis ( RA ). We investigated the therapeutic potential of rebamipide, a gastroprotective agent with a property of reactive oxygen species scavenger, on the development of inflammatory polyarthritis and the pathophysiological mechanisms by which rebamipide might confer anti‐arthritic effects in SKG mice, an animal model of RA . Intraperitoneal (i.p.) injection of rebamipide attenuated the severity of clinical and histological arthritis. Rebampide treatment reduced the number of T helper type 1 ( T h1), T h2, T h17, inducible T cell co‐stimulator ( ICOS ) + follicular helper T ( T fh) transitional type (T2) and mature B cells in the spleen, but increased the number of regulatory T ( T reg ), CD 19 + CD 1d high CD 5 high , CD 19 + CD 25 high forkhead box protein 3 ( F oxP3) + regulatory B ( B reg ) cells, memory B cells, and transitional type 1 (T1) B cells. In addition, flow cytometric analysis revealed significantly decreased populations of FAS + GL ‐7 + germinal centre B cells and B 220 − CD 138 + plasma cells in the spleens of rebamipide‐treated SKG mice compared to controls. Rebamipide decreased germinal centre B cells and reciprocally induced B reg cells in a dose‐dependent manner in vitro . Rebamipide‐induced B reg cells had more suppressive capacity in relation to T cell proliferation and also inhibited T h17 differentiation from murine CD 4 + T cells. Together, these data show that i.p. administration of rebamipide suppresses arthritis severity by inducing B reg and T reg cells and suppressing T fh and T h17 cells in a murine model of RA .