Studies on the induction of pathogenic T cell by endoplasmic reticulum stress and the pathogenesis of systemic lupus erythematosus

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: 株式会社膠原病研究所
• Principal Investigator: Tsumiyama Ken 株式会社膠原病研究所, 研究部, 主任研究員 (20514607)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 全身性エリテマトーデス（SLE） / 小胞体ストレス / CD4 T細胞

Outline of Final Research Achievements

We examined the involvement of endoplasmic reticulum (ER) stress in the induction of pathogenic T cell that causes systemic lupus erythematosus (SLE). We found that when SLE was induced in mice, the expression of unfolded protein response (UPR)-related molecules was increased in CD4 T cells. In these CD4 T cells, the gene expression of several molecules related to Wnt signaling pathway was changed. In vivo administration of ER stress inducer accelerated the production of autoantibody and autoimmune tissue injury. The result suggests that ER stress contributes to the pathogenesis of SLE by modulating the function of T cell.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、難病であるSLEの発症機序の一端を明らかにすることができた。この中で、細胞の恒常性を維持する機構である小胞体ストレス応答がT細胞の変調を引き起こし、SLEの病態形成に関与することを示した。これにより、小胞体ストレス応答関連分子を標的としたSLEの治療の可能性を示すことができたと考える。