Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2019 Oct 25;366(6464). doi: 10.1126/science.aax6624.
How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.
早期定植和随后接触微生物群如何影响长期组织免疫仍知之甚少。在这里，我们表明粘膜相关不变 T (MAIT) 细胞的发育依赖于特定的时间窗口，此后 MAIT 细胞的发育会永久受损。这种印记取决于早期生活中接触到合成来自核黄素的抗原的特定微生物。在成年人中，皮肤 MAIT 细胞是产生白细胞介素-17A (IL-17A) 的淋巴细胞的主要群体，它们表现出独特的转录特征，并可以随后以白细胞介素-1 (IL-1)、白细胞介素-18 (IL-18) 和抗原依赖的方式对皮肤共生菌作出反应。因此，皮肤 MAIT 细胞的局部激活促进了伤口愈合。总之，我们的工作揭示了特定的微生物群成员与 MAIT 细胞之间的特权相互作用，这种相互作用依次控制组织印迹和随后对损伤的反应。
