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Int Immunol. 2014 Oct;26(10):551-61. doi: 10.1093/intimm/dxu057. Epub 2014 May 22.

Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell.

Author information

1
Laboratory for Immune Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 230-0045 Kanagawa, Japan The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021 Jilin, People's Republic of China.
2
Laboratory for Immune Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 230-0045 Kanagawa, Japan.
3
Laboratory for Immune Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 230-0045 Kanagawa, Japan Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 102-0076 Tokyo, Japan.
4
Laboratory for Developmental Genetics, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 230-0045 Kanagawa, Japan.
5
The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021 Jilin, People's Republic of China.
6
Laboratory for Immune Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 230-0045 Kanagawa, Japan taniguti@rcai.riken.jp.

Abstract

NKT cells are characterized by their expression of an NKT-cell-specific invariant antigen-receptor α chain encoded by Vα14Jα18 gene segments. These NKT cells bridge the innate and acquired immune systems to mediate effective and augmented responses; however, the limited number of NKT cells in vivo hampers their analysis. Here, two lines of induced pluripotent stem cell-derived mice (NKT-iPSC-derived mice) were generated by reprogramming of mature NKT cells, where one harbors both rearranged Vα14Jα18 and Vβ7 genes and the other carries rearranged Vα14Jα18 on both alleles but germline Vβ loci. The analysis of NKT-iPSC-derived mice showed a significant increase in NKT cell numbers with relatively normal frequencies of functional subsets, but significantly enhanced in some cases, and acquired functional NKT cell maturation in peripheral lymphoid organs. NKT-iPSC-derived mice also showed normal development of other immune cells except for the absence of γδT cells and disturbed development of conventional CD4 αβT cells. These results suggest that the NKT-iPSC-derived mice are a better model for NKT cell development and function study rather than transgenic mouse models reported previously and also that the presence of a pre-rearranged Vα14Jα18 in the natural chromosomal context favors the developmental fate of NKT cells.

KEYWORDS:

NKT cell; TCR rearrangement; iPSC

PMID:
24854340
PMCID:
PMC4169672
DOI:
10.1093/intimm/dxu057
[Indexed for MEDLINE]
Free PMC Article
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