Activated Mucosal-associated Invariant T Cells Have a Pathogenic Role in a Murine Model of Inflammatory Bowel Disease.
Activated Mucosal-associated Invariant T Cells Have a Pathogenic Role in a Murine Model of Inflammatory Bowel Disease.
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DOI：
10.1016/j.jcmgh.2021.08.018
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发表时间：
2022
影响因子：
7.2
通讯作者：
Miyake S
中科院分区：
文献类型：
--
作者：
Yasutomi Y;Chiba A;Haga K;Murayama G;Makiyama A;Kuga T;Watanabe M;Okamoto R;Nagahara A;Nagaishi T;Miyake S
粘膜相关不变T细胞(MAIT)是受主要组织相容性复合体相关分子1(MR1)限制的先天T细胞，表达半不变T细胞受体。此前，我们报道了溃疡性结肠炎(UC)患者循环中MAIT细胞的激活状态与疾病活动性有关，这些细胞已渗透到炎症的结肠粘膜。这些发现表明MAIT细胞参与了炎症性肠病的发病机制。我们利用缺乏MAIT细胞和合成拮抗剂MR1配体的mr1−/−小鼠，研究了mtat细胞在结肠炎发病机制中的作用。恶唑酮结肠炎模型为−/−小鼠(背景为C57BL/6)及其窝仔野生型对照，C57BL/6小鼠口服拮抗剂异丁基-6-甲酰蝶呤(I6-FP)。分析I6-FP对小鼠脾细胞和结肠固有层淋巴细胞产生细胞因子的影响。对mr1、−/−和i6-FP处理的小鼠及其对照小鼠的肠道通透性进行了评估。观察I6-FP对UC患者MAIT细胞产生细胞因子的影响。MR1缺乏或I6-FP治疗可降低恶唑酮结肠炎的严重程度。I6-FP治疗减少了小鼠和UC患者MAIT细胞中细胞因子的产生。虽然MR1缺乏增加了小鼠的肠道通透性，但I6-FP给药不影响小鼠的肠道完整性。这些结果表明MAIT细胞在结肠炎中起致病作用，抑制MAIT细胞的激活可能会在不影响肠道完整性的情况下减轻结肠炎的严重程度。因此，MAIT细胞是包括UC在内的炎症性肠病的潜在治疗靶点。
Mucosal-associated invariant T (MAIT) cells are innate-like T cells restricted by major histocompatibility complex-related molecule 1 (MR1) and express a semi-invariant T cell receptor. Previously, we reported the activation status of circulating MAIT cells in patients with ulcerative colitis (UC) was associated with disease activity and that these cells had infiltrated the inflamed colonic mucosa. These findings suggest MAIT cells are involved in the pathogenesis of inflammatory bowel disease. We investigated the role of MAIT cells in the pathogenesis of colitis by using MR1−/− mice lacking MAIT cells and a synthetic antagonistic MR1 ligand. Oxazolone colitis was induced in MR1−/− mice (C57BL/6 background), their littermate wild-type controls, and C57BL/6 mice orally administered an antagonistic MR1 ligand, isobutyl 6-formyl pterin (i6-FP). Cytokine production of splenocytes and colonic lamina propria lymphocytes from mice receiving i6-FP was analyzed. Intestinal permeability was assessed in MR1−/− and i6-FP-treated mice and their controls. The effect of i6-FP on cytokine production by MAIT cells from patients with UC was assessed. MR1 deficiency or i6-FP treatment reduced the severity of oxazolone colitis. i6-FP treatment reduced cytokine production in MAIT cells from mice and patients with UC. Although MR1 deficiency increased the intestinal permeability, i6-FP administration did not affect gut integrity in mice. These results indicate MAIT cells have a pathogenic role in colitis and suppression of MAIT cell activation might reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells are potential therapeutic targets for inflammatory bowel disease including UC.
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DOI：
10.1084/jem.20142110
发表时间：
2015-06-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rahimpour A;Koay HF;Enders A;Clanchy R;Eckle SB;Meehan B;Chen Z;Whittle B;Liu L;Fairlie DP;Goodnow CC;McCluskey J;Rossjohn J;Uldrich AP;Pellicci DG;Godfrey DI
通讯作者：
Godfrey DI
影响因子：
29.4
作者：
Sharma D;Malik A;Guy CS;Karki R;Vogel P;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
4.9
作者：
Hiejima, Eitaro;Kawai, Tomoki;Heike, Toshio
通讯作者：
Heike, Toshio
影响因子：
32.4
作者：
Lee JS;Tato CM;Joyce-Shaikh B;Gulen MF;Cayatte C;Chen Y;Blumenschein WM;Judo M;Ayanoglu G;McClanahan TK;Li X;Cua DJ
通讯作者：
Cua DJ