Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23

Yu Xu, Yang Sun, Hao Shen, Yuling Dai, Haifeng Liu, Ronghong Li, Hongdao Zhang, Ligang Wu, Xiaoyan Zhu and Xiaolong Liu ()
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Yu Xu: University of Chinese Academy of Sciences
Yang Sun: University of Chinese Academy of Sciences
Hao Shen: University of Chinese Academy of Sciences
Yuling Dai: University of Chinese Academy of Sciences
Haifeng Liu: University of Chinese Academy of Sciences
Ronghong Li: University of Chinese Academy of Sciences
Hongdao Zhang: University of Chinese Academy of Sciences
Ligang Wu: University of Chinese Academy of Sciences
Xiaoyan Zhu: University of Chinese Academy of Sciences
Xiaolong Liu: University of Chinese Academy of Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+ double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.

Date: 2018
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DOI: 10.1038/s41467-018-06372-1

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