1. MAIT cells are imprinted by the microbiota in early life and promote tissue repair
- Author
-
Constantinides, Michael G, Link, Verena M, Tamoutounour, Samira, Wong, Andrea C, Perez-Chaparro, P Juliana, Han, Seong-Ji, Chen, Y Erin, Li, Kelin, Farhat, Sepideh, Weckel, Antonin, Krishnamurthy, Siddharth R, Vujkovic-Cvijin, Ivan, Linehan, Jonathan L, Bouladoux, Nicolas, Merrill, E Dean, Roy, Sobhan, Cua, Daniel J, Adams, Erin J, Bhandoola, Avinash, Scharschmidt, Tiffany C, Aubé, Jeffrey, Fischbach, Michael A, and Belkaid, Yasmine
- Subjects
Clinical Research ,Vaccine Related ,1.1 Normal biological development and functioning ,Underpinning research ,Inflammatory and immune system ,Animals ,Bacteria ,Germ-Free Life ,Histocompatibility Antigens Class I ,Humans ,Interleukin-1 ,Interleukin-17 ,Interleukin-18 ,Interleukin-23 ,Mice ,Mice ,Inbred BALB C ,Mice ,Inbred C57BL ,Mice ,Knockout ,Microbiota ,Minor Histocompatibility Antigens ,Mucosal-Associated Invariant T Cells ,Riboflavin ,Skin ,Specific Pathogen-Free Organisms ,Wound Healing ,General Science & Technology - Abstract
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.
- Published
- 2019