The elucidation of the function of resident memory T cells in graft-versus-host disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16276
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of Tsukuba
• Principal Investigator: KUBOTA Noriko 筑波大学, 医学医療系, 講師 (10844847)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 移植片対宿主病 / レジデントメモリーT細胞 / CD122

Outline of Final Research Achievements

Antigen-stimulated naive T cells differentiate into effector and memory T cells, of which resident memory T (TRM) cells reside permanently in organ tissues. Involvement of TRM cells has been indicated in pathological conditions of various skin diseases. CD122, which is the β chain subunit of interleukin (IL)-2 and IL-15 receptors, is expressed on immune cells including TRM cells. We performed experiments to investigate whether CD122 signaling in skin CD8+ TRM cells mediates the development of cutaneous graft-versus-host disease (GVHD). We elucidated that particularly skin memory CD8+ T cells mediate the development of skin GVHD, and blockade of CD122 may be an effective treatment strategy for skin GVHD.

Free Research Field

免疫アレルギー

Academic Significance and Societal Importance of the Research Achievements

我々は皮膚GVHDモデルマウスを用いた研究において、移入したドナーT細胞の一部が皮膚TRMとなって皮膚に残存し、慢性化して持続した皮膚症状を形成し、皮膚の線維化に関与していることを解明した。さらにその機序は、抗CD122抗体の投与で抑制されることを証明した。慢性化する皮膚自己免疫疾患のプロトタイプである、皮膚GVHDにおける皮膚TRMの機能を解明した報告はこれまでになく、CD122が、皮膚GVHDに対する新たな治療ターゲットとなり得る可能性を示した。