The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group 3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA-dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and protective immunity.

肠道免疫系统必须能够对多种传染性生物作出反应，同时保持对非病原微生物和食物抗原的耐受性。维生素A代谢物全反式-视黄酸（atRA）参与了这种平衡的调节，部分是通过调节肠道中的先天淋巴样细胞（ILC）反应。然而，依赖atRA的肠道免疫和体内平衡的分子机制仍然难以捉摸。在这里，我们定义了转录抑制因子在癌症1（HIC1，ZBTB29）中的甲基化在肠道中ILC反应的调节中的作用。肠道ILC以维生素A依赖的方式表达HIC1。在没有HIC1的情况下，产生IL-22的第3组ILC（ILC3）丢失，导致对细菌性病原体啮齿类柠檬酸杆菌感染的敏感性增加。因此，ILC3s中HIC1的atRA依赖性表达可调节肠内稳态和保护性免疫。