Early-life microbial exposure imprints the abundance of mucosal-associated invariant T cells and subsequent interactions modulate their function

How early exposure to the microbiota impacts long-term host immunity remains poorly understood. Here we show that the development of mucosal-associated invariant T (MAIT) cells depends on early-life exposure to microbes that synthesize riboflavin, such as Enterobacteriaceae. This microbial imprinting relies on a specific temporal window, after which MAIT cell development is permanently impaired. In adults, MAIT cells are a dominant population of IL-17A-producing lymphocytes within the skin that can subsequently respond to skin commensals in an IL-1 and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing and limits skin inflammation. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells that sequentially controls both tissue-imprinting and subsequent response to injury and inflammation.

宿主早期菌群暴露如何影响长期宿主免疫，目前仍未得到充分阐明。本研究表明，黏膜相关恒定T细胞（mucosal-associated invariant T, MAIT）的发育，依赖于生命早期接触能够合成核黄素的微生物，例如肠杆菌科（Enterobacteriaceae）。这种微生物印记依赖于特定的时间窗口，在此窗口之后，MAIT细胞的发育将受到永久性损伤。在成体中，MAIT细胞是皮肤内占主导地位的IL-17A分泌型淋巴细胞群，后续可通过IL-1依赖且抗原依赖的方式，对皮肤共生微生物产生应答。因此，皮肤MAIT细胞的局部活化可促进伤口愈合，并抑制皮肤炎症。综上，本研究揭示了特定菌群成员与MAIT细胞之间的独特互作关系，该互作可依次调控组织印记以及后续对损伤与炎症的应答。