The elusidation of depelopment and maintenance mechanism of skin resident memory T cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08299
• 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: Osaka University
• Principal Investigator: Watanabe Rei 大阪大学, 大学院医学系研究科, 招へい教授 (60463866)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Resident memory T細胞

Outline of Final Research Achievements

In this research project, we focused on the involvement of FABP4/FABP5, which show enhanced expression in skin resident memory T cells (TRM). We analyzed the mechanisms underlying the development and maintenance of TRM in human skin and murine models. In human skin, it was found that with aging, especially epidermal TRM increased in number, and expression intensity of FABP5 in both the epidermal and dermal TRM was elevated. Several TRM-related molecules were identified that correlated with the intensity of FABP5 expression and could explore cascades linking FABP5 to these molecules. In the murine model, TRM-mediated contact hypersensitivity reaction was attenuated in FABP5-deficient mice, indicating that while FABP5 does not affect the construction of TRM-like cells, it is involved in their effector function and local maintenance.

Free Research Field

皮膚免疫

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、細胞内脂肪酸キャリアタンパクであるFABP5が特にTRMのエフェクター機能、局所維持に関わることが判明し、皮膚においては外用剤による皮膚TRMのFABP5発現制御が皮膚TRMのエフェクター機能・局所維持の制御に結びつく可能性が考えられた。例えば皮膚局所感染症においては、FABP5の発現促進が、TRMのエフェクター機能促進による感染制御、局所維持による予防効果につながる可能性が期待される一方、TRMが関わる多くの臓器特異的な免疫疾患においてはFABP5の発現抑制が疾患コントロールにつながる可能性が考えられ、本研究成果の、FABP5を標的とした疾患治療への応用が期待される。