PT  - JOURNAL ARTICLE
AU  - Kyle Burrows
AU  - Frann Antignano
AU  - Michael Bramhall
AU  - Alistair Chenery
AU  - Sebastian Scheer
AU  - Vladimir Korinek
AU  - T. Michael Underhill
AU  - Colby Zaph
TI  - The transcriptional repressor HIC1 regulates intestinal immune homeostasis
AID  - 10.1101/083873
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 083873
4099  - http://biorxiv.org/content/early/2016/10/27/083873.short
4100  - http://biorxiv.org/content/early/2016/10/27/083873.full
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.