HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis

Kyle Burrows, Frann Antignano, Alistair Chenery, Michael Bramhall, Vladimir Korinek, T. Michael Underhill, Colby Zaph

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group 3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA-dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and protective immunity.

Original languageEnglish
Article numbere1006869
Number of pages15
JournalPLoS Pathogens
Volume14
Issue number2
DOIs
Publication statusPublished - 22 Feb 2018

Keywords

  • gastrointestinal tract
  • cell-mediated immunity
  • T cells
  • bacterial diseases
  • homeostasis
  • infectious disease immunology
  • diet
  • colon

Cite this

Burrows, Kyle ; Antignano, Frann ; Chenery, Alistair ; Bramhall, Michael ; Korinek, Vladimir ; Underhill, T. Michael ; Zaph, Colby. / HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis. In: PLoS Pathogens. 2018 ; Vol. 14, No. 2.
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HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis. / Burrows, Kyle; Antignano, Frann; Chenery, Alistair; Bramhall, Michael; Korinek, Vladimir; Underhill, T. Michael; Zaph, Colby.

In: PLoS Pathogens, Vol. 14, No. 2, e1006869, 22.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

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