T cell surveillance mechanisms in peripheral tissues

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyoto University
• Principal Investigator: EGAWA GYOHEI 京都大学, 医学研究科, 講師 (50511812)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: T cell / homeostatic expansion / skin / homeostasis

Outline of Final Research Achievements

In this study, we aimed to elucidate how T cells infiltrate into non-inflamed skin using "homeostatic expansion" model. In this model, T cells proliferated markedly by 7 days after transfer, and many T cells migrated to the skin without inflammation. Almost all proliferated T cells were memory-phenotype (CD44+) and showed a tendency to differentiate into Th1 and Th17. In vivo imaging showed that CD8+ T cells infiltrated into the epidermis, especially around the hair follicles, and remained in the skin for more than 60 days. Dermatitis developed spontaneously when regulatory T cells are excluded during T cell transfer.

Free Research Field

Dermatology

Academic Significance and Societal Importance of the Research Achievements

抗原非特異的にT細胞が増殖するHomeostatic expansionという現象は、生理的には新生児期、骨髄移植後、免疫抑制状態（AIDS患者や免疫抑制剤使用患者）からの回復時などで見られる。これらの状態では、新生児中毒性紅斑、脂漏性皮膚炎、好酸球性膿疱性毛包炎、免疫再構築症候群（IRIS）などの病態が生じることが知られる。本研究の成果からこれらの病態では炎症のない皮膚へのT細胞浸潤が増加し、host-parasite relationshipの変化が生じることが示唆された。この現象のメカニズム解明が進めば、これらの病態を制御する新たな治療標的などへとつながる可能性がある。