The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function During Intestinal Infection

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

3 Scopus Citations
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Author(s)

  • Xianzhi Gao
  • Xin Shen
  • Kuai Liu
  • Ying Fan
  • Qianying Xu
  • Xiaoyu Meng
  • Shenghui Hong
  • Zhengwei Huang
  • Xia Liu
  • Linrong Lu
  • Lie Wang

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number939033
Journal / PublicationFrontiers in Immunology
Volume13
Online published1 Jul 2022
Publication statusPublished - Jul 2022

Link(s)

Abstract

Innate lymphoid cells (ILCs) have been identified as a heterogeneous population of lymphocytes that mirrors the cytokine and transcriptional profile of adaptive T cells. The dynamic balance between key transcription factors determines the heterogeneity, plasticity, and functions of ILC subsets. The transcription factor ThPOK is highly conserved in biological evolution and exerts pivotal functions in the differentiation of T cells. However, the function of ThPOK in ILC3s has not been identified. Here, we found that ThPOK regulated the homeostasis of ILC3s, as mice lacking ThPOK showed decreased NKp46+ ILC3s and increased CCR6- NKp46- ILC3s. ThPOK-deficient mice were more sensitive to S. typhimurium infection due to the impaired IFN-γ secretion of NKp46+ ILC3s. Furthermore, ThPOK participates in ILC3-mediated control of C. rodentium infection by negatively regulating IL-17A secretion. ThPOK preserves the identity of NKp46+ ILC3s by repressing RORγt, which indirectly releases T-bet expression. On the molecular level, ThPOK directly binds to Rorc and Il23r to restrain their expression which further modulates IL-17A secretion. Collectively, our analysis revealed a critical role of ThPOK in the homeostasis and functions of ILC3 subsets.

Research Area(s)

  • homeostasis, ILC3s, mucosa, ThPOK, transcription factor

Citation Format(s)

The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function During Intestinal Infection. / Gao, Xianzhi; Shen, Xin; Liu, Kuai et al.
In: Frontiers in Immunology, Vol. 13, 939033, 07.2022.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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