Mechanism of differentiation of intraepithelial lymphocytes with anti-inflammatory properties.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Keio University
• Principal Investigator: KEIKO Ono 慶應義塾大学, 医学部(信濃町), 助教 (50645611)
• Co-Investigator(Kenkyū-buntansha): 筋野 智久 慶應義塾大学, 医学部(信濃町), 講師 (40464862)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸管上皮間リンパ球 / 転写因子 / 炎症性腸疾患

Outline of Final Research Achievements

Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. CD4+CD8αα+ IELs, a subset of IELs that express CD4 and CD8α, exhibit regulatory properties against intestinal inflammation. Their reduced abundance in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, has been reported.
We investigated the differentiation mechanisms of anti-inflammatory IELs to elucidate the pathology of inflammatory bowel diseases and to consider the development of new treatments.
In this study, we focused on the fact that anti-inflammatory IELs exist only between the intestinal epithelium, and analyzed the differentiation mechanism from the perspective of IEL dynamics, focusing on CCR9.

Free Research Field

腸管免疫

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患は遺伝的要因、環境因子、免疫学的要因、腸内細菌が関与する多因子疾患であることがわかっているが、根本的な治療法がなく、発症原因の解明と新規治療法開発が急務である。現在存在する治療薬はCD4T細胞活性を抑制する免疫調節薬が主体であり、IELに着目した治療法は存在しない。炎症抑制性IELの分化機構を明らかにすることで、これまでの既存の治療法とは異なるアプローチの創薬開発に繋がる可能性がある。