Elucidation of the regulation mechanisms of maturation and TCR repertoire of small intestinal interepithelial lymphocytes by Notch signaling

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15191
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIFUNE Chieko 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (80632645)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: Notchシグナル / 腸管上皮間リンパ球

Outline of Final Research Achievements

To elucidate the molecules that regulate the maturation of TCRγδCD8ααIELs, we conducted DNA microarray and proteomic analysis of TCRγδCD8ααIELs, revealing expression changes in various functional molecule-related genes. Additionally, single-cell RNA sequencing analysis of TCRγδCD8ααIELs showed the emergence of clusters with high expression of molecule A in Rbpj-8 knockout mice. TCRγδCD8ααIELs were further subdivided into three IEL subsets using Thy1.2 and molecule A markers, and Rbpj-8 knockout resulted in an increased proportion of the subset with enhanced activation and proliferation potential. Therefore, these findings suggest the potential involvement of Notch signaling in the activation of TCRγδCD8ααIELs.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

TCRγδ型CD8ααIELsは腸管の恒常性や、腸炎の抑制に重要な上皮間リンパ球の一種でり、これまで、種々の分子がTCRγδ型CD8ααIELsの分化調節に関連している報告はいくつかなされているが、TCRγδ型CD8ααIELsの成熟や活性化状態を調節する分子機構については、ほとんど明らかではなかった。本研究はNotchシグナルが、TCRγδ型CD8ααIELsの多様性や活性化状態を制御していることを示唆する知見を見出したことから、今後の解析により腸炎の病態制御に重要な手掛かりとなる可能性がある。