靶向黏膜相关恒定T细胞或可治疗IBD
创作:Ferryman 审核:aluba 09月07日
  • 在恶唑酮诱导的结肠炎小鼠模型中可观察到MAIT细胞的活化,而敲除MR1(缺失MAIT细胞)可缓解小鼠的结肠炎症状并提高生存率;
  • 利用MR1配体i6-FP抑制MAIT细胞的活性,可减少后者的促炎因子(IFN-γ、TNF-α等)产生,同时降低了γδ T细胞、iNKT细胞及CD4+ T细胞产生的促炎因子,从而缓解恶唑酮诱导的小鼠结肠炎;
  • i6-FP不影响正常小鼠肠道完整性,但可降低UC患者的循环MAIT细胞的促炎因子产生。
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aluba
黏膜相关恒定T(MAIT)细胞是一种先天样T细胞,表达主要组织相容性复合体相关分子1(MR1)及半恒定的TCR。之前的研究发现,溃疡性结肠炎(UC)患者炎症结肠粘膜中可观察到循环MAIT细胞的浸润,且后者的活化状态与疾病活动度相关。CMGH Cellular and Molecular Gastroenterology and Hepatology上发表的一项最新研究结果,发现缺失MAIT细胞或抑制MAIT细胞活化可降低MAIT细胞的促炎因子产生,从而缓解恶唑酮诱导的小鼠结肠炎。该研究结果提示,MAIT细胞或可作为IBD的治疗靶点。
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Activated mucosal-associated invariant T cells have a pathogenic role in a murine model of inflammatory bowel disease

活化的黏膜相关恒定T细胞在IBD小鼠模型中具有致病作用

10.1016/j.jcmgh.2021.08.018

08-28, Article

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BACKGROUND AND AIMS: 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 (IBD). 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.
METHODS: 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 UC patients was assessed.
RESULTS: 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.
CONCLUSIONS: 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 IBD including UC.

First Authors:
Yusuke Yasutomi

Correspondence Authors:
Asako Chiba,Sachiko Miyake

All Authors:
Yusuke Yasutomi,Asako Chiba,Keiichi Haga,Goh Murayama,Ayako Makiyama,Taiga Kuga,Mamoru Watanabe,Ryuichi Okamoto,Akihito Nagahara,Takashi Nagaishi,Sachiko Miyake

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