Omenetti Sara, Pizarro Theresa T
Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH , USA.
Front Immunol. 2015 Dec 17;6:639. doi: 10.3389/fimmu.2015.00639. eCollection 2015.
T-helper 17 (Th17) and T-regulatory (Treg) cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 cells and Tregs share similar developmental requirements. In fact, the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6, and all-trans retinoic acid. Importantly, the intestinal microbiome also provides immunostimulatory signals, which can activate innate and downstream adaptive immune responses. Specific components of the gut microbiome have been implicated in the production of proinflammatory cytokines by innate immune cells, such as IL-6, IL-23, IL-1β, and the subsequent generation and expansion of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of intestinal Tregs that can actively induce mucosal tolerance. As such, dysbiosis of the gut microbiome may not solely represent a consequence of gut inflammation, but rather shape the Treg/Th17 commitment and influence susceptibility to inflammatory bowel disease. In this review, we discuss Treg and Th17 cell plasticity, its dynamic regulation by the microbiome, and highlight its impact on intestinal homeostasis and disease.
辅助性T细胞17（Th17）和调节性T细胞（Treg）常见于屏障表面，尤其是肠道黏膜内，它们在那里分别发挥保护宿主免受病原微生物侵害以及抑制效应T细胞过度反应的作用。尽管Th17细胞和Tregs具有不同的功能特性，但它们有着相似的发育需求。事实上，初始抗原T细胞向Th17或Treg谱系的分化命运受到包括转化生长因子β（TGFβ）、白细胞介素-6（IL-6）和全反式维甲酸等关键介质的精细调控。重要的是，肠道微生物群也提供免疫刺激信号，可激活先天性和下游适应性免疫反应。肠道微生物群的特定成分与先天性免疫细胞产生促炎细胞因子有关，如IL-6、IL-23、IL-1β，以及随后Th17细胞的产生和扩增。同样，共生细菌及其代谢产物也可促进肠道Tregs的产生，这些Tregs可积极诱导黏膜耐受性。因此，肠道微生物群失调可能不仅仅是肠道炎症的结果，而是会影响Treg/Th17的分化，并影响炎症性肠病的易感性。在本综述中，我们讨论了Treg和Th17细胞的可塑性、微生物群对其的动态调节，并强调了其对肠道稳态和疾病的影响。
