Analysis of CD4-CD8alphabeta-TCRalphabeta+ T cells as anergic antigen presenting cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07938
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nemoto Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (20456213)
• Co-Investigator(Kenkyū-buntansha): 岡本 隆一 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 炎症性腸疾患 / 腸管粘膜免疫 / DNT細胞 / 抗原提示 / 腸管上皮間リンパ球

Outline of Final Research Achievements

Previously, we found that CD4-CD8-TCRαβ+ double negative T (DNT) cells function as tolerogenic antigen-presenting cells and are involved in the pathogenesis of Crohn's disease. In the present study, we analyzed the mechanism by which DNT cells acquire antigen-presenting capacity, searched for its regulators and analyzed in detail the immunosuppressive mechanism of DNT cells.
We found that loss of T-cell-specific MHC-II not only exacerbates acute colitis, but also small intestinal ulcers and chronic colitis, and that Peyer's patches play an important role in the expression of MHC-II on DNT cells.

Free Research Field

腸管免疫

Academic Significance and Societal Importance of the Research Achievements

腸管粘膜における抗原取り込み経路における研究としてはCX3CR1+マクロファージが腸管上皮細胞層のタイトジャンクションに樹状突起を挿入し、直接管腔抗原を捕捉するという驚くべき経路 (Rescigno M et al, Nat Immunol 2001)、上皮細胞層に点在し、粘液を産生する杯細胞が低分子抗原を取り込み、粘膜内のCD103+樹状細胞に引き渡すという経路 (McDole JR et al, Nature 2013)があるが、本経路はそれに勝るユニークな発見である。