小柯机器人

美国康奈尔大学Gregory F. Sonnenberg团队发现ZBTB46 定义和调节保护肠道的 ILC3。这一研究成果于2022年7月13日发表在国际顶尖学术期刊《自然》上。

他们以单细胞分辨率定义肠道中的所有 RORγt+ 免疫细胞，并确定表达 ZBTB46 的第 3 组先天淋巴细胞 (ILC3s) 的一个亚群，ZBTB46 是一种指定常规树突状细胞的转录因子。 ZBTB46 由 CCR6+ 淋巴组织诱导剂样 ILC3 强烈表达，其在发育和表型上与常规树突细胞不同，其表达受 RORγt 印记，由微生物群来源信号微调并由促炎细胞因子增加。ZBTB46 抑制 ILC3 的炎症特性，包括 T 辅助 17 细胞的 OX40L 依赖性扩增和肠道感染后发生的肠道炎症加剧。

最后，ZBTB46+ ILC3 是 IL-22 的主要来源，该群体的选择性耗竭使小鼠易受肠道感染和相关肠道炎症的影响。这些结果表明 ZBTB46 是一种在常规树突细胞和 ILC3 之间共享的转录因子，并确定了 ZBTB46 在抑制 ILC3 的促炎特性方面的细胞内在功能，以及 ZBTB46+ ILC3 在协调肠道健康中的非冗余作用。

据了解，RORγt 是一种谱系特异性转录因子，由富含胃肠道的免疫细胞表达，可促进免疫、炎症和组织稳态。然而，关于这些细胞类型之间的细胞异质性、控制保护性与炎症性特性的机制及其功能冗余等基本问题仍然存在。

附：英文原文

Title: ZBTB46 defines and regulates ILC3s that protect the intestine

Author: Zhou, Wenqing, Zhou, Lei, Zhou, Jordan, Chu, Coco, Zhang, Chao, Sockolow, Robbyn E., Eberl, Gerard, Sonnenberg, Gregory F.

Issue&Volume: 2022-07-13

Abstract: RORγt is a lineage-specifying transcription factor that is expressed by immune cells that are enriched in the gastrointestinal tract and promote immunity, inflammation and tissue homeostasis1,2,3,4,5,6,7,8,9,10,11,12,13,14,15. However, fundamental questions remain with regard to the cellular heterogeneity among these cell types, the mechanisms that control protective versus inflammatory properties and their functional redundancy. Here we define all RORγt+ immune cells in the intestine at single-cell resolution and identify a subset of group 3 innate lymphoid cells (ILC3s) that expresses ZBTB46, a transcription factor specifying conventional dendritic cells16,17,18,19,20. ZBTB46 is robustly expressed by CCR6+ lymphoid-tissue-inducer-like ILC3s that are developmentally and phenotypically distinct from conventional dendritic cells, and its expression is imprinted by RORγt, fine-tuned by microbiota-derived signals and increased by pro-inflammatory cytokines. ZBTB46 restrains the inflammatory properties of ILC3s, including the OX40L-dependent expansion of T helper 17 cells and the exacerbated intestinal inflammation that occurs after enteric infection. Finally, ZBTB46+ ILC3s are a major source of IL-22, and selective depletion of this population renders mice susceptible to enteric infection and associated intestinal inflammation. These results show that ZBTB46 is a transcription factor that is shared between conventional dendritic cells and ILC3s, and identify a cell-intrinsic function for ZBTB46 in restraining the pro-inflammatory properties of ILC3s and a non-redundant role for ZBTB46+ ILC3s in orchestrating intestinal health.

DOI: 10.1038/s41586-022-04934-4

Source: https://www.nature.com/articles/s41586-022-04934-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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