AUTHOR=Chen Binfeng , Ye Baokui , Li Mengyuan , Wang Shuyi , Li Jin , Lai Yimei , Yang Niansheng , Ke Zunfu , Zhang Hui 

TITLE=TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A–Producing CD4+ Tissue-Resident Memory T Cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.931761

DOI=10.3389/fimmu.2022.931761

ISSN=1664-3224

ABSTRACT=Tissue-resident memory T cells (TRM cells) have been shown to play an instrumental role in providing local immune responses for pathogen clearance in barrier tissues. However, their contribution to inflammatory bowel diseases (IBDs) and the underlying regulation are less clear. Here, we identified a critical role of TIGIT in regulating CD4+ TRM cells in an experimental model of intestinal inflammation. CD4+ TRM cell signature was enriched in mice with DSS-induced colitis. Phenotypically, these CD4+ TRM cells could be classified into CD69+CD103- and CD69+CD103+ subsets. Functionally, these CD4+ TRM cells were heterogeneous. CD69+CD103- CD4+ TRM cells were proinflammatory and produced IFNγ and IL-17A, which accounted for 68.7% and  62.9% of total IFNγ+ and IL-17A+ CD4+ T cells respectively, while CD69+CD103+ CD4+ TRM cells accounted for 73.7% Foxp3+ regulatory T cells. TIGIT expression was increased in CD4+ T cells in the gut of mice with DSS-induced colitis. TIGIT deficiency impaired IL-17A expression in CD69+CD103- CD4+ TRM cells specifically, resulting in ameliorated gut inflammation and tissue injury. Together, this study provides new insights into the regulation of gut inflammation that TIGIT deficiency protects mice from DSS-induced colitis, which might have potential therapeutic value in the treatment of IBDs.