Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection

Xiaohuan Guo, Ju Qiu, Tony Tu, Xuanming Yang, Liufu Deng, Robert A. Anders, Liang Zhou, Yang Xin Fu

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Inhibitors of the transcription factor STAT3 target STAT3-dependent tumorigenesis but patients often develop diarrhea from unknown mechanisms. Herewe showed that STAT3 deficiency increased morbidity and mortality after Citrobacter rodentium infection with decreased secretion of cytokines including IL-17 and IL-22 associated with the transcription factor RORγt. Administration of the cytokine IL-22 was sufficient to rescue STAT3-deficient mice from lethal infection. Although STAT3 was required for IL-22 production in both innate and adaptive arms, by using conditional gene-deficient mice, we observed that STAT3 expression in RORγt+ innate lymphoid cells (ILC3s), but not Tcells, was essential for the protection. However, STAT3 was required for RORγt expression in T helper cells, but not in ILC3s. Activated STAT3 could directly bind tothe Il22 locus. Thus, cancer therapies that utilize STAT3 inhibitors increase the risk for pathogen-mediated diarrhea through direct suppression of IL-22 from gut ILCs.

Original languageEnglish (US)
Pages (from-to)25-39
Number of pages15
JournalImmunity
Volume40
Issue number1
DOIs
StatePublished - Jan 16 2014

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STAT3 Transcription Factor
Lymphocytes
Infection
Diarrhea
Citrobacter rodentium
Cytokines
Interleukin-17
Helper-Inducer T-Lymphocytes
Carcinogenesis
Transcription Factors
Morbidity
Mortality
interleukin-22
Genes
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. / Guo, Xiaohuan; Qiu, Ju; Tu, Tony; Yang, Xuanming; Deng, Liufu; Anders, Robert A.; Zhou, Liang; Fu, Yang Xin.

In: Immunity, Vol. 40, No. 1, 16.01.2014, p. 25-39.

Research output: Contribution to journalArticle

Guo, Xiaohuan ; Qiu, Ju ; Tu, Tony ; Yang, Xuanming ; Deng, Liufu ; Anders, Robert A. ; Zhou, Liang ; Fu, Yang Xin. / Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. In: Immunity. 2014 ; Vol. 40, No. 1. pp. 25-39.
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