The transcriptional repressor HIC1 regulates intestinal immune homeostasis
The transcriptional repressor HIC1 regulates intestinal immune homeostasis
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DOI：
10.1038/mi.2017.17
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发表时间：
2017-11-01
影响因子：
8
通讯作者：
Zaph, C.
中科院分区：
文献类型：
--
作者：
Burrows, K.;Antignano, F.;Zaph, C.
肠道是一个独特的免疫环境，必须对感染性生物做出反应，但对肠道微生物和食物抗原保持耐受性。然而，调节肠道免疫细胞功能的分子机制仍不清楚。在这里，我们确定了POK/ZBTB家族转录因子在癌症中高甲基化1（ZBTB 29）作为肠道免疫和炎症的中心组成部分。在稳定状态下，BMP 1在肠固有层（LP）中的免疫细胞中特异性表达，并且具有BMP 1的T细胞特异性缺失的小鼠在LP中具有减少的T细胞数量。维生素A代谢产物视黄酸调节BMP 1的表达，因为维生素A缺乏饮食的小鼠在肠道中缺乏BMP 1阳性细胞。在体外和体内，IL-17缺陷型T细胞过度产生IL-17 A，并且不能诱导肠道炎症，从而确定了在稳态和炎症条件下，IL-17 1在调节肠道微环境中的T细胞功能中的关键作用。
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.