Analysis of pathogenicity and development of novel therapy byinflammation-regulating proteins in systemic autoimmune diseases

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We reported previously that autoantibodies to calpastatin (inhibitor of calpain (calcium-dependent neutral proteinase)) and follistatin-related protein (FRP) are found in patients with rheumatoid arthritis. Since these target antigens appeared to show regulatory effects against inflammation, we have intended to clarify the possibility that arthritis may be treated by regulating these autoantigens and autoantibodies. Calpastatin inhibited not only the secretion of IL -6 from fibroblasts, but also affected T cell differentiation, in particular strongly suppress ed the differentiation and activation of Th17 cell. Although FRP has been debated to show different action on regulating of inflammation between human and mouse, we demonstrated that FRP activates inflammation in natural immunity system via TLR4 -CD14 signaling. Analyses of these inflammation-regulating proteins may clarify the pathogenic mechanisms and novel therapeutic strategies of inflammatory arthritis and autoimmune diseases