The transcriptional repressor HIC1 regulates intestinal immune homeostasis

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)


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
Issue number6
Publication statusPublished - 1 Nov 2017
Externally publishedYes


Dive into the research topics of 'The transcriptional repressor HIC1 regulates intestinal immune homeostasis'. Together they form a unique fingerprint.

Cite this