Functional analysis of heparin/heparan sulfate on regulation of B cell inhibitory receptor CD72

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17695
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: AKATSU Chizuru 東京医科歯科大学, 難治疾患研究所, 助教 (60735984)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 免疫学 / B細胞 / 自己免疫 / レクチン / CD72 / 硫酸化糖鎖

Outline of Final Research Achievements

CD72 is an inhibitory receptor mainly expressed in B cells and contains C-type lectin-like domain (CTLD) in its extracellular region. CD72 recognizes Sm/RNP, an SLE-related self antigen, through its CTLD and negatively regulates B cell response to Sm/RNP and inhibits SLE development. In this study, we revealed that CD72 recognizes various sulfated glycans besides Sm/RNP, and inhibits antibody production to the glycans. Furthermore, endocytosis of CD72 was regulated by the glycan ligands. These results suggested that inhibitory function of CD72 is regulated by its sulfated glycan ligands in B cells.

Free Research Field

糖鎖生物学、免疫学

Academic Significance and Societal Importance of the Research Achievements

CD72はB細胞上に発現する抑制性の分子であり、日本での患者数が6-10万人と比較的有病率の高い自己免疫疾患であるSLEの発症を抑制する分子である。本研究によりCD72が硫酸化糖鎖を認識し、硫酸化糖鎖による機能制御を受けることが示唆されたことで、SLEの新たな治療法の開発に向けてCD72の機能を人為的に制御するための新たなターゲットが示された。