Mice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases. These models help elucidate the mechanisms underlying the disease and in the development of novel therapies. However, if mice are deficient in certain cells and/or effectors associated with human diseases, how can their functions be investigated in this species? Mucosal-associated invariant T (MAIT) cells, a novel innate-like T cell family member, are a good example. MAIT cells are abundant in humans but scarce in laboratory mice. MAIT cells harbor an invariant T cell receptor and recognize nonpeptidic antigens vitamin B2 metabolites from bacteria and yeasts. Recent studies have shown that MAIT cells play a pivotal role in human diseases such as bacterial infections and autoimmune and inflammatory diseases. MAIT cells possess granulysin, a human-specific effector molecule, but granulysin and its homologue are absent in mice. Furthermore, MAIT cells show poor proliferation in vitro. To overcome these problems and further our knowledge of MAIT cells, we have established a method to expand MAIT cells via induced pluripotent stem cells (iPSCs). In this review, we describe recent advances in the field of MAIT cell research and our approach for human disease modeling with iPSC-derived MAIT cells.

中文翻译：

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来自诱导性多能干细胞的与粘膜相关的恒定T细胞：一种模拟人类疾病的新方法。

小鼠经常被用来模拟涉及免疫失调的人类疾病，例如自身免疫性疾病和炎性疾病。这些模型有助于阐明该疾病的潜在机制以及新型疗法的发展。但是，如果小鼠缺乏与人类疾病相关的某些细胞和/或效应子，如何在该物种中研究其功能？粘膜相关的不变T（MAIT）细胞，一种新型的先天性T细胞家族成员，就是一个很好的例子。MAIT细胞在人类中很丰富，但在实验室小鼠中却很少。MAIT细胞具有不变的T细胞受体，可以识别细菌和酵母中的非肽抗原维生素B2代谢产物。最近的研究表明，MAIT细胞在人类疾病（如细菌感染，自身免疫和炎性疾病）中起着关键作用。MAIT细胞具有人类特殊的效应分子颗粒溶素，但小鼠中却没有颗粒溶素及其同源物。此外，MAIT细胞在体外显示出较差的增殖。为了克服这些问题并进一步了解MAIT细胞，我们建立了一种通过诱导多能干细胞（iPSC）扩增MAIT细胞的方法。在这篇综述中，我们描述了MAIT细胞研究领域的最新进展以及我们使用iPSC衍生的MAIT细胞进行人类疾病建模的方法。