Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Immunity. 2013 Aug 22;39(2):386-99. doi: 10.1016/j.immuni.2013.08.002. Epub 2013 Aug 15.
Aryl hydrocarbon receptor (Ahr) is crucial for the maintenance and function of group 3 innate lymphoid cells (ILCs), which are important in gut immunity. Because Ahr promotes T helper 17 (Th17) cell differentiation in vitro, it is reasonable to expect that Ahr would enhance Th17 cells in vivo. Instead, we show that Ahr deficiency caused increased intestinal Th17 cells, raising the possibility that group 3 ILCs could negatively regulate Th17 cells. Reduced innate interleukin-22 (IL-22) in Ahr-deficient mice allowed expansion of commensal segmented filamentous bacteria (SFB), known to promote Th17 cells. Compared to Rorc(+/+)Ahr(-/-) mice, Rorc(gfp/+)Ahr(-/-) mice had further reduced group 3 ILCs and were prone to spontaneous colitis with increased SFB and Th17 cells. Innate expression of Ahr played a protective role in T-cell-mediated experimental colitis by suppressing pathogenic Th17 cells. Our data reveal an intricate balance between ILCs and Th17 cells regulated by Ahr and commensal flora.
芳香烃受体（Ahr）对于维持和功能发挥至关重要 3 组固有淋巴细胞（ILCs），在肠道免疫中很重要。因为 Ahr 在体外促进辅助性 T 细胞 17（Th17）细胞分化，所以可以合理地预期 Ahr 会增强体内 Th17 细胞。相反，我们发现 Ahr 缺陷导致肠道 Th17 细胞增加，这增加了 3 组 ILC 可能负调控 Th17 细胞的可能性。Ahr 缺陷小鼠中先天白细胞介素-22（IL-22）减少，允许共生的分段丝状菌（SFB）扩张，已知 SFB 促进 Th17 细胞。与 Rorc(+/+)Ahr(-/-) 小鼠相比，Rorc(gfp/+)Ahr(-/-) 小鼠的 3 组 ILC 进一步减少，并且易自发发生结肠炎，SFB 和 Th17 细胞增加。先天表达的 Ahr 通过抑制致病性 Th17 细胞在 T 细胞介导的实验性结肠炎中发挥保护作用。我们的数据揭示了 Ahr 和共生菌群调节的 ILCs 和 Th17 细胞之间复杂的平衡。
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