Regulation of regulatory T cell trafficking by targeting glycans

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19542
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Chiba University
• Principal Investigator: KAWASHIMA Hiroto 千葉大学, 大学院薬学研究院, 教授 (50260336)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 制御性T細胞 / リンパ球ホーミング / アレルギー性疾患 / 抗糖鎖抗体 / L-セレクチン

Outline of Final Research Achievements

Nasal-associated lymphoid tissue (NALT) is a mucosal lymphoid tissue that functions as a border of defense against inhaled antigens as well as nasal allergic responses. Lymphocyte homing to NALT is mediated by the interaction between L-selectin on lymphocytes and specific glycans on high endothelial venules (HEV) in NALT. We previously generated an anti-glycan monoclonal antibody S2 which recognizes glycans specifically expressed on HEV. In this study, we found that S2 administration suppressed homing of naive lymphocytes and induced the accumulation of Treg cells in NALT. Consequently, S2 administration to ovalbumin (OVA)-immunized mice resulted in the amelioration of nasal symptoms and reduction of OVA-specific serum IgE. The expression of Th2-related cytokines was also significantly diminished after S2 administration in the OVA-immunized mice. Taken together, these results suggest that S2 would be useful for the treatment of allergic rhinitis.

Free Research Field

免疫学、生化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、独自開発したS2抗体が、NALTへの制御性T細胞の選択的な蓄積を誘導するとともにマウスアレルギー性鼻炎を有意に抑制するユニークな活性を持つ抗糖鎖抗体であることを見出した。アレルギー性鼻炎の治療には対症療法が広く用いられているが、本研究の成果は、制御性T細胞の体内動態の人為的制御に基づくアレルギー性疾患の根本的な治療法の開発に繋がる知見として重要と考えられる。