Immunological analysis of glucose intolerance induced by hyperactivated dendritic cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08902
• 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: Gunma University
• Principal Investigator: KANEKO YORIAKI 群馬大学, 医学部附属病院, 講師 (00334095)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 樹状細胞 / ホスファターゼ / Shp-1 / 2型糖尿病

Outline of Final Research Achievements

Abnormalities of the immune system are associated with the development of type 2 diabetes (T2D). In this project, we tried to analyze the contribution of a cytoplasmic tyrosine phosphatase Shp-1 expressed on dendritic cells (DC) in the pathogenesis of T2D. Shp-1 CKO the conditional knockout mice, which lack Shp-1 specifically in DC, had a mild degree of glucose intolerance and had mild data abnormalities related to glycolipid metabolism when they were subjected to a high-fat diet (HFD). Increased production of IL-10, an anti-inflammatory cytokine, and increased sugar consumption in the spleen are considered as possible mechanisms for the resistance of Shp-1 CKO to HFD-induced glucose intolerance.

Free Research Field

免疫学、腎臓病学、リウマチ学

Academic Significance and Societal Importance of the Research Achievements

CD11cを発現するDCやマクロファージにおいてShp-1を欠損させると、高脂肪食を負荷しても耐糖能の悪化が少ないことがコンディショナルノックアウトマウスの解析から明らかになった。今回の解析を通じて、CD11cを発現する細胞のShp-1を標的とした治療法が直ちに開発できる可能性は少ないと思われたが、IL-10をターゲットにする治療法の開発を探索するなど、本研究課題を通じてT2Dの病態解明や治療法の開発における端緒が得られた。