TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A-Producing CD4(+) Tissue-Resident Memory T Cells.
TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A-Producing CD4(+) Tissue-Resident Memory T Cells.
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TIGIT缺陷通过调节产生il - 17a的CD4（+）组织驻留记忆T细胞来保护小鼠免受dss诱导的结肠炎。
DOI：
10.3389/fimmu.2022.931761
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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组织驻留记忆T细胞（TRM细胞）已被证明在屏障组织中提供病原体清除的局部免疫应答中发挥重要作用。然而，它们对炎症性肠病（IBD）的贡献和潜在的调控尚不清楚。在这里，我们确定了具有免疫球蛋白和ITIM的T细胞免疫受体（TIGIT）在肠道炎症实验模型中调节CD 4 + TRM细胞的关键作用。我们发现，在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠中，CD 4 + TRM细胞增加，并与疾病活动相关。表型上，这些CD 4 + TRM细胞可分为CD 69 + CD 103 −和CD 69 + CD 103+亚群。在功能上，这些CD 4 + TRM细胞是异质性的。CD 69 + CD 103 − CD 4 + TRM细胞是促炎细胞，产生干扰素-γ（IFNγ）和白细胞介素-17A（IL-17 A），分别占总IFNγ+和IL-17 A + CD 4 + T细胞的68.7%和62.9%，而CD 69 + CD 103 + CD 4 + TRM细胞占Foxp 3+调节性T细胞的73.7%。在患有DSS诱导的结肠炎的小鼠的肠道中的CD 4 + T细胞中TIGIT表达增加。TIGIT缺陷特异性地损害了CD 69 + CD 103 − CD 4 + TRM细胞中的IL-17 A表达，从而导致肠道炎症和组织损伤的改善。总之，这项研究为肠道炎症的调节提供了新的见解，即TIGIT缺乏可保护小鼠免受DSS诱导的结肠炎，这可能在IBD的治疗中具有潜在的治疗价值。
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 T-cell immunoreceptor with immunoglobulin and ITIM (TIGIT) in regulating CD4+ TRM cells in an experimental model of intestinal inflammation. We found that CD4+ TRM cells were increased and correlated with disease activities in mice with dextran sulfate sodium (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 pro-inflammatory and produced interferon-γ (IFNγ) and interleukin-17A (IL-17A), which accounted for 68.7% and 62.9% of total IFNγ+ and IL-17A+ CD4+ T cells, respectively, whereas 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 a potential therapeutic value in the treatment of IBDs.