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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2016; 8(4): 158-169
Published online Apr 26, 2016. doi: 10.4252/wjsc.v8.i4.158
Mucosal-associated invariant T cells from induced pluripotent stem cells: A novel approach for modeling human diseases
Chie Sugimoto, Hiroyoshi Fujita, Hiroshi Wakao
Chie Sugimoto, Hiroyoshi Fujita, Hiroshi Wakao, Department of Hygiene and Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
Author contributions: All authors contributed to interpreting the collected data and writing the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hiroshi Wakao, PhD, Department of Hygiene and Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, N15W7 Kita-ku, Sapporo 060-8638, Japan. hwakao@med.hokudai.ac.jp
Telephone: +81-11-7065066 Fax: +81-11-7067819
Received: June 17, 2015
Peer-review started: June 20, 2015
First decision: August 14, 2015
Revised: September 17, 2015
Accepted: February 14, 2016
Article in press: February 16, 2016
Published online: April 26, 2016
Processing time: 300 Days and 19.3 Hours
Abstract

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.

Keywords: Mucosal-associated invariant T cells; Induced pluripotent stem cells; Differentiation; Adoptive transfer; Inflammatory diseases; Autoimmune diseases; Disease modeling; Infectious diseases; Immunocompromised mouse

Core tip: Mucosal-associated invariant T (MAIT) cells, a novel innate-like T cell subset abundant in humans, play a pivotal role in immune-dysregulated diseases. However, MAIT cells are quite rare in laboratory mice and show poor proliferation in vitro. This makes it difficult to delineate their physiological functions in health and disease. Therefore, we developed a method to generate human MAIT cells from induced pluripotent stem cells [redifferentiation of MAIT (reMAIT) cells]. Given that reMAIT cells harbor characteristics quasi-identical to those found in MAIT cells from human peripheral blood, they will be useful to model human diseases in animals.