Group 3 innate lymphoid cells (ILC3s) play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation. The transcription factor PLZF (promyelocytic leukemia zinc finger), encoded by zinc finger BTB domain containing 16 (Zbtb16), is highly and transiently expressed in ILC precursors (ILCPs). However, the role of PLZF in regulating ILC3 development and function remains unknown. Here, we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets. PLZF was dispensable for ILC3 development. However, PLZF deficiency in ILC3s resulted in increased innate interleukin-22 (IL-22) secretion and protection against gut infection and inflammation. Mechanistically, PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression. Together, our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.

第 3 组先天淋巴细胞 (ILC3) 通过保护宿主免受病原体感染和组织炎症，在维持肠道稳态方面发挥着重要作用。转录因子 PLZF（早幼粒细胞白血病锌指）由含有 16 ( Zbtb16 ) 的锌指 BTB 结构域编码，在 ILC 前体 (ILCP) 中高度瞬时表达。然而，PLZF 在调节 ILC3 发育和功能中的作用仍不清楚。在这里，我们发现与其他 ILC 亚群相比，PLZF 在成熟肠道 ILC3 中特异性表达。 PLZF 对于 ILC3 开发来说是可有可无的。然而，ILC3 中的 PLZF 缺陷导致先天性白细胞介素 22 (IL-22) 分泌增加，并能预防肠道感染和炎症。从机制上讲，PLZF 通过与 IL-22 启动子区域结合进行转录抑制，以细胞固有的方式负调节 ILC3 的 IL-22 表达。总之，我们的数据表明 PLZF 限制肠道 ILC3 功能以调节肠道免疫稳态。