研究代表者らはシェーグレン症候群の病態に関与しているB細胞活性化因子（BAFF）がその受容体（BR３）と結合しイオンチャンネルを介した経路で単球やB細胞を活性化することを見出し、イオンチャンネルを同定しこの機序を阻害する化合物を得た。当該化合物はin vitroで患者単球上のイオンチャンネルを介して単球でのBAFF-BR3シグナルを阻害することによりB細胞の活性化を抑制し、自己免疫疾患モデルマウスでの自己抗体産生を抑制し、病態を軽減することが明らかとなった。さらに当該化合物の構造類似体はin vitroにおけるBAFFによる単球やB細胞の活性化に対してより強い抑制作用を有する知見が得られた。
BAFF and its receptor (BR3) are involved in the pathogenesis of Sjogren's syndrome (SS). We demonstrated that the expression levels of BR3 and a voltage-gated sodium channel in SS monocytes were significantly higher than those of healthy controls and that elevation was correlated with serum IgG level of the patients. In addition, we have successfully discovered a low molecular weight compound which has inhibitory activities against both BAFF signaling pathways and a sodium channel. In this study, we tested the effects of this compound on production of autoantibodies and inflammatory cytokines by using autoimmune model mice. As a results, we found that this compound inhibited production of anti- sDNA antibody and inflammatory cytokines, such as IL-6 and IL-10. Moreover, this compound also suppressed infiltration of B cells into the organs, such as lachrymal glands and kidney. Notably, we have found a novel compound which is expected more efficacy on the suppression of B cell function.

研究種目 : 基盤研究 (C) (一般)
研究期間 : 2016～2018
課題番号 : 16K09905 
研究分野 : 免疫学
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