The transcriptional repressor HIC1 regulates intestinal immune homeostasis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
128090
CIHR - Canada
MOP-89773
CIHR - Canada
MOP-106623
CIHR - Canada
PubMed
28327618
DOI
10.1038/mi.2017.17
PII: S1933-0219(22)00751-6
Knihovny.cz E-resources
- MeSH
- Homeostasis MeSH
- Immunity MeSH
- Interleukin-17 metabolism MeSH
- Cells, Cultured MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Gene Expression Regulation MeSH
- Repressor Proteins metabolism MeSH
- Mucous Membrane physiology MeSH
- Intestines physiology MeSH
- T-Lymphocytes physiology MeSH
- Kruppel-Like Transcription Factors genetics metabolism MeSH
- Tretinoin metabolism MeSH
- Inflammation immunology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hic1 protein, mouse MeSH Browser
- Interleukin-17 MeSH
- Repressor Proteins MeSH
- Kruppel-Like Transcription Factors MeSH
- Tretinoin MeSH
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.
Infection and Immunity Program Monash Biomedicine Discovery Institute Clayton Victoria Australia
The Biomedical Research Centre University of British Columbia Vancouver British Columbia Canada
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