Regulation immune responses by the interaction between DCIR and its ligand

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: KAIFU Tomonori 東北医科薬科大学, 医学部, 講師 (90343037)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: DCIR / Ｃ型レクチン受容体 / アシアロ糖鎖 / 樹状細胞

Outline of Final Research Achievements

Dysfunction of DCIR (Dendritic Cell ImmunoReceptor), an inhibitory C-type lectin, has shown to develop autoimmune-like diseases and disorders of bone metabolism. The understanding of DCIR-mediated regulation contributes to the comprehension of the pathogenesis for these disorders. We have succeeded to identify the functional DCIR ligand, resulting in the establishment of basic knowledge to understand the mechanisms underlying immune regulation by the interaction of DCIR and its ligand. Here, we showed the expression pattern of enzymes that modify the quantity of DCIR ligand in various cells. In addition, the in vivo and in vitro treatment of the enzyme capable of increasing DCIR ligand suppressed immune responses. The possible way to control DCIR-mediated signaling will contribute to the development of a new therapy for autoimmune and bone metabolic diseases.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

自然免疫受容体であるDCIRは免疫システムや骨代謝の恒常性を維持する重要な受容体のひとつである。本研究において糖鎖末端の構造を認識する受容体において、末端構造を糖鎖修飾酵素により変化させ受容体機能を発揮させることに成功した。糖鎖修飾酵素の発現様式やDCIR-リガンドの相互作用が免疫応答を負に調節する仕組みが明らかとなりDCIR制御の基礎的知見が得られた。DCIRは関節リウマチ等の自己免疫疾患と関与することが示されており、DCIRを標的としいた医薬成分は新たな治療法の開発につながると期待している