Department of Gastroenterology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou, China.
Center for Infection and Immunity, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2021 Mar 11;12:626017. doi: 10.3389/fimmu.2021.626017. eCollection 2021.
Mucosal associated invariant T (MAIT) cells play a critical role in ()-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in -positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in -induced gastritis, which may provide potential targeting strategies for gastritis treatment.
黏膜相关恒定 T(MAIT)细胞通过促进黏膜炎症和加重黏膜损伤在()诱导的胃炎中发挥关键作用(1,2)。然而,其潜在机制和涉及的关键分子仍不清楚。在这里,我们确定 OX40,一种主要表达在 T 细胞上的共刺激分子,是促进 MAIT 细胞增殖和 IL-9 产生并促进阳性胃炎患者黏膜炎症的关键调节因子。血清检查显示胃炎患者的 IL-9 水平升高。同时,黏膜 MAIT 细胞中 OX40 的表达增加,与健康对照组相比,胃炎患者黏膜树突状细胞(DC)中 OX40L 的表达也上调。进一步的结果表明,OX40/OX40L 通路的激活促进了 MAIT 细胞的 IL-9 产生,并且 MAIT 细胞在 OX40 和 OX40L 的交联后显示出高度激活的表型。此外,MAIT 细胞产生的 IL-9 水平与胃黏膜的炎症指标呈正相关,提示 IL-9 产生的 MAIT 细胞在黏膜炎症中可能发挥潜在作用。综上所述,我们阐明了 OX40/OX40L 轴在()诱导的胃炎中促进黏膜 MAIT 细胞增殖和 IL-9 产生,这可能为胃炎治疗提供潜在的靶向策略。