title: Expansion of functional human mucosal-associated invariant T cells via reprogramming to pluripotency and redifferentiation.
abstract: Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor Vα7.2, CD161, and interleukin-18 receptor chain α. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.
authors.affiliation: Department of Environmental Biology, School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. hwakao@med.hokudai.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakao
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yoshikiyo
authors.forename: Uichi
authors.initials: U
authors.lastname: Koshimizu
authors.forename: Tomoko
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kei
authors.initials: K
authors.lastname: Enomoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yasutomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minakami
authors.forename: Jyunji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Rika
authors.initials: R
authors.lastname: Wakao
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Tadashi
authors.initials: T
authors.lastname: Udagawa
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Kazue
authors.initials: K
authors.lastname: Higuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.forename: Manami
authors.initials: M
authors.lastname: Ohtaka
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujita
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009092:Mucous Membrane / Q000166:cytology* / Q000378:metabolism; D009161:Mycobacterium / Q000276:immunology; D009164:Mycobacterium Infections / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism