The transcriptional repressor HIC1 regulates intestinal immune homeostasis

Kyle Burrows, F. Antignano, M Bramhall, A. Chenery, S Scheer, V. Korinek, T. M. Underhill, C Zaph

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP. HIC1 expression is regulated by the Vitamin A metabolite retinoic acid, as mice raised on a Vitamin A-deficient diet lack HIC1-positive cells in the intestine. HIC1-deficient T cells overproduce IL-17A in vitro and in vivo, and fail to induce intestinal inflammation, identifying a critical role for HIC1 in the regulation of T-cell function in the intestinal microenvironment under both homeostatic and inflammatory conditions.

Original languageEnglish
Pages (from-to)1518-1528
Number of pages11
JournalMucosal Immunology
Volume10
Issue number6
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

Burrows, Kyle ; Antignano, F. ; Bramhall, M ; Chenery, A. ; Scheer, S ; Korinek, V. ; Underhill, T. M. ; Zaph, C. / The transcriptional repressor HIC1 regulates intestinal immune homeostasis. In: Mucosal Immunology. 2017 ; Vol. 10, No. 6. pp. 1518-1528.
@article{118ea386bd704b8c9123de7a757f1710,
title = "The transcriptional repressor HIC1 regulates intestinal immune homeostasis",
abstract = "The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP. HIC1 expression is regulated by the Vitamin A metabolite retinoic acid, as mice raised on a Vitamin A-deficient diet lack HIC1-positive cells in the intestine. HIC1-deficient T cells overproduce IL-17A in vitro and in vivo, and fail to induce intestinal inflammation, identifying a critical role for HIC1 in the regulation of T-cell function in the intestinal microenvironment under both homeostatic and inflammatory conditions.",
author = "Kyle Burrows and F. Antignano and M Bramhall and A. Chenery and S Scheer and V. Korinek and Underhill, {T. M.} and C Zaph",
year = "2017",
month = "11",
day = "1",
doi = "10.1038/mi.2017.17",
language = "English",
volume = "10",
pages = "1518--1528",
journal = "Mucosal Immunology",
issn = "1935-3456",
publisher = "Nature Publishing Group",
number = "6",

}

The transcriptional repressor HIC1 regulates intestinal immune homeostasis. / Burrows, Kyle; Antignano, F.; Bramhall, M; Chenery, A.; Scheer, S; Korinek, V.; Underhill, T. M.; Zaph, C.

In: Mucosal Immunology, Vol. 10, No. 6, 01.11.2017, p. 1518-1528.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The transcriptional repressor HIC1 regulates intestinal immune homeostasis

AU - Burrows, Kyle

AU - Antignano, F.

AU - Bramhall, M

AU - Chenery, A.

AU - Scheer, S

AU - Korinek, V.

AU - Underhill, T. M.

AU - Zaph, C

PY - 2017/11/1

Y1 - 2017/11/1

N2 - The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP. HIC1 expression is regulated by the Vitamin A metabolite retinoic acid, as mice raised on a Vitamin A-deficient diet lack HIC1-positive cells in the intestine. HIC1-deficient T cells overproduce IL-17A in vitro and in vivo, and fail to induce intestinal inflammation, identifying a critical role for HIC1 in the regulation of T-cell function in the intestinal microenvironment under both homeostatic and inflammatory conditions.

AB - The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP. HIC1 expression is regulated by the Vitamin A metabolite retinoic acid, as mice raised on a Vitamin A-deficient diet lack HIC1-positive cells in the intestine. HIC1-deficient T cells overproduce IL-17A in vitro and in vivo, and fail to induce intestinal inflammation, identifying a critical role for HIC1 in the regulation of T-cell function in the intestinal microenvironment under both homeostatic and inflammatory conditions.

UR - http://www.scopus.com/inward/record.url?scp=85031762087&partnerID=8YFLogxK

U2 - 10.1038/mi.2017.17

DO - 10.1038/mi.2017.17

M3 - Article

VL - 10

SP - 1518

EP - 1528

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1935-3456

IS - 6

ER -