Application to the treatment of canine atopic dermatitis based on the mechanism of the retention of skin memory T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K15980
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kyoto University
• Principal Investigator: Asahina Ryota 京都大学, 医学研究科, 特別研究員(PD) (00837487)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: アトピー性皮膚炎 / 組織常在型記憶T細胞 / 樹状細胞

Outline of Final Research Achievements

Experiments were conducted to elucidate the mechanism of retention of CD4+ tissue-resident memory T (TRM) cells in allergic dermatitis. In a mouse model of delayed-type hypersensitivity, CD4+TRM cells co-localized with classical dendritic cell type 2 (cDC2) in perivascular clusters. In addition, cDC2 highly produced CXCL16, and administration of a CXCL16-neutralizing antibody decreased the number and cluster formation of CD4+TRM cells. Furthermore, CXCR6-positive CD4+TRM cells were pathogenic TRM cells that produced cytokines to induce a rapid relapse upon antigen re-exposure. These findings were also observed in a mouse model of atopic dermatitis.

Free Research Field

皮膚免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、アレルギー性皮膚炎におけるCD4+TRM細胞の皮膚駐在に関わるCXCL16を介した真皮樹状細胞とのクロストーク機構を明らかにした。また、再燃誘導において中心的な役割を果たす病原性TRM細胞サブセットとして、CXCR6陽性CD4+TRM細胞を新たに同定した。以上より、CD4+TRM細胞によるアトピー性皮膚炎の再燃病態が明らかになった。今後は、CXCR6/CXCL16を標的としたCD4+TRM細胞の駐在制御に基づいたアトピー性皮膚炎に対する新規治療開発に応用されることが期待される。