Mechanism of gdT cell activation by immunoreceptor CD96

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Kyoko Hayashi (大岡杏子) 筑波大学, 革新的創薬開発研究センター, 研究員 (50569019)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: γδT細胞 / 免疫受容体 / 抗体医療 / 乾癬

Outline of Final Research Achievements

CD96 is an immunoreceptor which functions as an activating or inhibitory receptor is controversial, although it is reported to be expressed on lymphoid cells and to regulate their activation. However, the function of CD96 on γδ T cells has not been clarified. We induced psoriasis in Rag1-deficient mice by transferring wild-type or CD96-deficient γδ T cells into their skin and showed that the disease was milder in mice with CD96-deficient γδ T cells. In addition, stimulation of γδ T cells isolated from the skin of wild-type mice with CD3 and CD96 antibodies in vitro experimental system enhanced IL-17 production upon IL-23 stimulation. These results indicate that CD96 on γδ T cells functions as an activation receptor.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

乾癬は慢性炎症性皮膚疾患であり、γδT細胞から産生されるIL-17Aが、病態の悪化に強く関与することが知られている。我々は、免疫受容体CD96がγδT細胞上に発現しており、γδT細胞の活性化受容体として機能していることを明らかにした。抗CD96中和抗体を投与したマウスでは、コントロール抗体を投与したマウスと比較して、真皮γδT細胞からのIL-17A産生が減少し、IMQ誘発皮膚炎が軽快した。つまり、CD96が乾癬治療のための潜在的な分子標的となりうることを見出した点に社会的意義がある。