Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Cell Host Microbe. 2010 Feb 18;7(2):140-50. doi: 10.1016/j.chom.2010.01.005.
IL-17 cytokine production by the Th17 T cell subset is regulated by intestinal commmensals. We show that microbial colonization also regulates innate IL-17 production. A population of CD62L(-) gamma/delta T cells, in particular a lineage expressing the IL-1 receptor 1 (IL-1R1), can be quickly activated by microbes to produce IL-17. Antibiotic treatment and monocolonization of mice suggest that specific commensals-but not metronidazole-sensitive anaerobes like Bacteroides species-are required for maintaining IL-1R1(+) gamma/delta T cells. Signaling through the guanine nucleotide exchange factor VAV1, but not through Toll-like receptors or antigen presentation pathways, is essential for inducing IL-1R1(+) gamma/delta T cells. Furthermore, IL-1R1(+) gamma/delta T cells are a potential source of IL-17 that can be activated by IL-23 and IL-1 in both infectious and noninfectious settings in vitro and in vivo. Thus, commensals orchestrate the expansion of phenotypically distinct gammadelta T cells, and innate immunity is a three-way interaction between host, pathogens, and microbiota.
IL-17 细胞因子由 Th17 T 细胞亚群产生，其受到肠道共生微生物的调节。我们发现，微生物定植也可调节固有 IL-17 的产生。特定的 CD62L(-)γ/δ T 细胞群体，尤其是表达白介素-1 受体 1（IL-1R1）的谱系，可以被微生物迅速激活产生 IL-17。抗生素处理和单菌定植实验表明，某些共生微生物而非甲硝唑敏感的厌氧菌（如拟杆菌属）对维持 IL-1R1(+)γ/δ T 细胞是必需的。G 蛋白交换因子 VAV1 的信号转导，而非 Toll 样受体或抗原呈递途径，对诱导 IL-1R1(+)γ/δ T 细胞是必不可少的。此外，IL-1R1(+)γ/δ T 细胞是一种潜在的 IL-17 来源，在体外和体内的感染和非感染环境中，其可以被 IL-23 和 IL-1 激活。因此，共生微生物协调表型不同的γ/δ T 细胞的扩增，固有免疫是宿主、病原体和微生物群落之间的三向相互作用。
