Investigation of molecular mechanism for serial transmission of tolerant status of T cells -Role of CD155 transducing signaling mediated by TIGIT-

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18041
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Juntendo University
• Principal Investigator: NEGISHI Naoko 順天堂大学, 大学院医学研究科, 特任助教 (40784294)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: TIGIT / トレランスの伝承 / 抗原特異的免疫寛容 / IL-2/IL-2レセプター / CD155

Outline of Final Research Achievements

In this study, we investigated how CD155-mediated signaling induce TIGIT expression in stimulated naive T cells, leading to suppressive function、based on the expression status of TIGIT, key molecules of “infectious tolerance”. we showed, CD3/CD155 double ligated T cells through IL-2/IL-2R - STAT5 axis by rapid expression of IL-2 which leads to the induction of downstream IL-2 expression inhibitory genes , resulting in IL-2 down reguration.　Additionally, we found that the upregulation of TIGIT expression in CD3/CD155 double ligated T cells occurs through rapid expression of IL-2.
We transfered TIGIT highly expressed on the tolerant T cells into recipent mouse, result in T cells from recipient mice were suppressed IL-2 expression.
Currently, We are going to confirm that the newly enhanced TIGIT is substantially from the past TIGIT expressing cells or newly stimulated and proliferated cells by using a reporter mouse strain taking advantage of TIGIT promoter-driven Cre recombinase.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、抑制性T細胞のTIGITの発現維持の証明が今まで困難であったin vitro及びin vivo系の両方を使った検証が可能となった。さらに、本研究成果は今まで不明であった免疫記憶の成立と維持機構の解明といった免疫発生学分野に重要な知見をもたらす。
本研究により、TIGITーCD155シグナルが免疫抑制機能を伝達に重要であることが明らかになったことで、TIGITーCD155をターゲットとした移植片に対する寛容誘導に関する細胞治療や診断法の開発、アレルギーや自己免疫疾患の治療開発にも重要な知見と情報をもたらす。