@article{dda709fef3274106a42c86bcdad57e47,
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 = "K. Burrows and F. Antignano and M. Bramhall and A. Chenery and S. Scheer and V. Korinek and Underhill, {T. M.} and C. Zaph",
note = "Funding Information: We thank C. Hunter, K. Jacobson, and S. Gerondakis for advice on the manuscript. We thank R. Dhesi, L. Rollins (BRC core), A. Johnson (UBCFlow), M. Williams (UBC AbLab), T. Murakami (BRC Genotyping), I. Barta (BRC Histology), and all members of BRC mouse facility for excellent technical assistance. This work was supported by the Canadian Institutes of Health Research{\textquoteright}s (CIHR) Canadian Epigenetics, Environment and Health Research Consortium (grant 128090 to C. Zaph) and operating grants (MOP-89773 and MOP-106623 to C. Zaph) and Australian National Health and Medical Research Council (NHMRC) project grants (APP1104433 and APP1104466 to C. Zaph). F. Antignano is the recipient of a CIHR/Canadian Association of Gastroenterology/Crohn{\textquoteright}s and Colitis Foundation of Canada postdoctoral fellowship. C. Zaph is a Michael Smith Foundation for Health Research Career Investigator and a veski innovation fellow. Publisher Copyright: {\textcopyright} 2017 Society for Mucosal Immunology.",
year = "2017",
month = nov,
day = "1",
doi = "10.1038/mi.2017.17",
language = "English",
volume = "10",
pages = "1518--1528",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "6",
}