The transcriptional repressor HIC1 regulates intestinal immune homeostasis |
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| Affiliation: | 1. The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada;2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada;3. Infection and Immunity Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia;4. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia;5. Department of Cell and Developmental Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic;6. Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada |
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| 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. |
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