康奈尔大学Gregory F. Sonnenberg研究团队揭示了ILC3s通过STING感知肠道微生物群，启动免疫耐受。相关论文于2025年6月16日发表在《免疫学》杂志上。

课题组人员在大肠的单细胞分辨率下分析了MHC II⁺细胞。在被病原体肝幽门螺杆菌定植后，第3组先天淋巴样细胞（ILC3s）是一个关键的RORγt⁺抗原呈递细胞，表达低水平的模式识别受体，但上调抗原呈递和STING信号的信号。小组发现，ILC3s中的STING信号可以直接感知微生物，并增强CCR7依赖性迁移到肠道引流淋巴结。ILC3-内源性STING信号支持微生物群特异性调节性T细胞的指令，抑制慢性炎症。

然而，肠道炎症诱导了旺盛的STING激活，导致ILC3s细胞死亡。他们的研究结果将STING定义为ILC3s中肠道微生物群的关键传感器。在稳定状态下，这使ILC3s具有指导免疫耐受的能力，但增强的STING激活变得有害并消除了这种组织保护细胞类型。

据悉，对肠道微生物群的免疫耐受对健康是必要的，但启动它的机制仍然是未知的。

附：英文原文

Title: ILC3s sense gut microbiota through STING to initiate immune tolerance

Author: Wenqing Zhou, Jordan Z. Zhou, Anees Ahmed, Myeong Joon Kim, Chun-Jun Guo, Gregory F. Sonnenberg

Issue&Volume: 2025-06-16

Abstract: Immune tolerance to gut microbiota is necessary for health, yet the mechanisms initiating it remain elusive. We profiled MHC II+ cells at single-cell resolution from the large intestine. Following colonization with the pathobiont Helicobacter hepaticus, group 3 innate lymphoid cells (ILC3s) were a key RORγt+ antigen-presenting cell that expressed low levels of pattern-recognition receptors but upregulated signatures for antigen presentation and STING signaling. We revealed that STING signaling in ILC3s permitted direct sensing of microbes and enhanced CCR7-dependent migration to gut-draining lymph nodes. ILC3-intrinsic STING signaling supported the instruction of microbiota-specific regulatory T cells and restrained chronic inflammation. However, gut inflammation induced exuberant STING activation, which resulted in the cell death of ILC3s. Our results define STING as a key sensor of gut microbiota in ILC3s. At steady state, this endows ILC3s with the ability to instruct immune tolerance, but heightened STING activation becomes detrimental and eliminates this tissue-protective cell type.

DOI: 10.1016/j.immuni.2025.05.016

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00237-7