Abstract Body

TSPAN32 is a member of the tetraspanin family, which is actively involved in the regulation of the immune responses. Previous studies have investigated the role of TSPAN32 in Multiple Sclerosis and Systemic Lupus Erythematosus, however no data are currently available about its role in Rheumatoid Arthritis (RA). In the present study, we have evaluated the expression levels of TSPAN32 in immune cells from a spontaneous mouse model of RA, the IL1ra knockout (KO) mouse, as well as in circulating and synovial-infiltrating immune cells from RA patients. TSPAN32 expression resulted significantly reduced in splenic CD4+ T cells from IL1ra KO mice, at 1 and 4 months of age. On the other hand, no significant modulation was observed for the other members of the tetraspanin family, with the exception of TSPAN4 and TSPAN31, which were significantly increased as compared to the wild-type mice. Along the same lines, a significant reduction in TSPAN32 expression was observed in CD4+ effector memory T cells from RA patients, as compared to healthy donors, and also a moderate but significant downregulation of TSPAN32 was observed in the inflammatory HLA-DR+CD27- cells from RA patients, as compared to those from OA patients. Overall, our data suggest that the reduced expression of TSPAN32 characterizes the pathogenetic T cell populations in RA, and that this may contribute to trigger the arthritogenic immune responses. Furthermore, our results strengthen the hypothesis that defective TSPAN32 expression may represent an important immunopathogenetic abnormality that could play a role in the pathogenesis of Th1/Th17-driven disorders.