Supplementary Material for: Activation, Deficiency, and Reduced IFN-γ Production of Mucosal-Associated Invariant T Cells in Patients with Inflammatory Bowel Disease

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can activate either in response to T-cell receptor (TCR) engagement or through activating cytokines and play an important role in autoimmune disorders. The study examined the level and function of MAIT cells in patients with inflammatory bowel disease (IBD). Circulating MAIT cell levels were significantly reduced in IBD patients. This MAIT cell deficiency was correlated with IBD disease activity grades, hemoglobin, and CRP. IFN-γ production of circulating MAIT cells in response to both MHC class 1b-like related protein (MR1)-dependent and -independent stimulations was decreased in IBD patients, which was partially associated with reduced activation of nuclear factor of activated T cells 1 (NFAT1) transcription factor, a main regulator of IFN-γ production. Expression levels of CD69, programmed death-1 (PD-1), and annexin V in MAIT cells were elevated in IBD patients. CCL20, CXCL10, CXCL16, and CCL25 were expressed higher in inflamed intestinal tissues than in noninflamed tissues. This study demonstrates that circulating MAIT cells are activated and numerically and functionally deficient in IBD patients. Furthermore, activated MAIT cells have the potential to migrate to inflamed tissues. These findings suggest an important role of MAIT cells in mucosal immunity in IBD.

黏膜相关恒定T细胞（Mucosal-associated invariant T cell, MAIT）是一类先天样T细胞，可通过T细胞受体（T-cell receptor, TCR）结合或激活型细胞因子通路被激活，在自身免疫性疾病中发挥重要作用。本研究针对炎症性肠病（inflammatory bowel disease, IBD）患者体内MAIT细胞的水平与功能展开了探究。炎症性肠病患者的循环MAIT细胞水平显著降低。该MAIT细胞缺乏程度与IBD的疾病活动度分级、血红蛋白水平及C反应蛋白（C-reactive protein, CRP）密切相关。炎症性肠病患者的循环MAIT细胞在受到主要组织相容性复合体I b类相关蛋白（MHC class 1b-like related protein, MR1）依赖与非依赖型刺激时，其干扰素-γ（interferon-γ, IFN-γ）的产生能力均出现下降，该现象部分与活化T细胞核因子1（nuclear factor of activated T cells 1, NFAT1）转录因子的激活受损相关，而NFAT1是调控IFN-γ产生的核心转录因子。炎症性肠病患者MAIT细胞表面CD69、程序性死亡受体1（programmed death-1, PD-1）及膜联蛋白V（annexin V）的表达水平均有所升高。趋化因子CCL20、CXCL10、CXCL16及CCL25在炎症肠道组织中的表达量显著高于非炎症肠道组织。本研究证实，炎症性肠病患者体内的循环MAIT细胞处于激活状态，且存在数量与功能上的双重缺陷。进一步研究发现，激活的MAIT细胞具备向炎症组织迁移的潜能。上述研究结果表明，MAIT细胞在炎症性肠病的黏膜免疫过程中发挥着重要作用。