Development of novel therapeutic strategies targeting cellular metabolism in autoimmune diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kobe University
• Principal Investigator: Saegusa Jun 神戸大学, 医学研究科, 准教授 (20514970)
• Co-Investigator(Kenkyū-buntansha): 森信 暁雄 神戸大学, 医学研究科, 准教授 (10294216) ; 河野 誠司 神戸大学, 医学部附属病院, 特命教授 (20351512)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 関節リウマチ / グルタミン代謝 / オートファジー / クロロキン / マウス関節炎モデル

Outline of Final Research Achievements

The glutamine metabolism inhibitor 6-diazo-5-oxo-L-norleucin (DON) and the mTOR inhibitor rapamycin suppressed T cell proliferation. In addition, the combined use of both showed a significantly stronger growth inhibitory effect than the case of a single agent. DON and rapamycin suppressed Th17 cell differentiation. DON suppressed the differentiation of bone marrow cells into dendritic cells and macrophages and promoted the differentiation into bone marrow-derived inhibitory cells (MDSC).
Furthermore, the effect of both drugs on suppressing mouse arthritis was examined. We demonstrated that combined treatment with rapamycin and DON additively ameliorated the arthritis in SKG mice, possibly by suppressing CD4+ T cell proliferation and Th17 differentiation.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

関節リウマチの病態には細胞内代謝異常が関わっており、グルタミン代謝阻害薬とmTOR阻害薬の併用療法は関節リウマチの新規治療法になり得ると考えられた。