@article{fbc727074c60436681e2c376eafa30ec,
title = "Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair",
abstract = "Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic immunity to the microbiota. Microbiota induce a form of adaptive immunity that couples antimicrobial function with tissue repair.",
keywords = "H2-M3, MHCIb, Staphylococcus epidermidis, microbiota, non-classical MHC class I, skin immunity, tissue repair",
author = "Linehan, {Jonathan L.} and Harrison, {Oliver J.} and Han, {Seong Ji} and Byrd, {Allyson L.} and Ivan Vujkovic-Cvijin and Villarino, {Alejandro V.} and Sen, {Shurjo K.} and Jahangheer Shaik and Margery Smelkinson and Samira Tamoutounour and Nicholas Collins and Nicolas Bouladoux and Amiran Dzutsev and Rosshart, {Stephan P.} and Arbuckle, {Jesse H.} and Wang, {Chyung Ru} and Kristie, {Thomas M.} and Barbara Rehermann and Giorgio Trinchieri and Brenchley, {Jason M.} and O'Shea, {John J.} and Yasmine Belkaid",
note = "Funding Information: This work was supported by the Division of Intramural Research of the NIAID, 1ZIAAI0011150 NCI, ZIABC01115309 NIAMS, ZIAAR04115910 and NIDDK ZIADK05451611. J.L.L. was supported by the NIGMS Postdoctoral Research Associate (PRAT) fellowship program. O.J.H. was supported by a National Psoriasis Foundation Early Career Research Grant. S.T. was supported by a Long-Term EMBO Fellowship. We thank the NIAID animal facility staff; the NIAID Microbiome Program gnotobiotic animal facility for the use of germ-free mice; K. Holmes, C. Eigsti, T. Hawley, and E. Stregevsky (NIAID Flow Cytometry facility); O. Schwartz (NIAID Biological Imaging facility), K. Beacht, J. LeGrand, and J. Davis for technical assistance; R. Bosselut for the B2m?/? mice; and H. Cantor for the Qa-1?/? mice. We thank the NIH tetramer core facility (Emory University) for provision of fMet peptide:H2-M3 tetramers. We thank all the members of the Belkaid laboratory for critically reading the manuscript and helpful discussions. Funding Information: This work was supported by the Division of Intramural Research of the NIAID , 1ZIAAI0011150 NCI , ZIABC01115309 NIAMS , ZIAAR04115910 and NIDDK ZIADK05451611 . J.L.L. was supported by the NIGMS Postdoctoral Research Associate ( PRAT ) fellowship program. O.J.H. was supported by a National Psoriasis Foundation Early Career Research Grant. S.T. was supported by a Long-Term EMBO Fellowship. We thank the NIAID animal facility staff; the NIAID Microbiome Program gnotobiotic animal facility for the use of germ-free mice; K. Holmes, C. Eigsti, T. Hawley, and E. Stregevsky (NIAID Flow Cytometry facility); O. Schwartz (NIAID Biological Imaging facility), K. Beacht, J. LeGrand, and J. Davis for technical assistance; R. Bosselut for the B2m −/− mice; and H. Cantor for the Qa-1 −/− mice. We thank the NIH tetramer core facility (Emory University) for provision of fMet peptide:H2-M3 tetramers. We thank all the members of the Belkaid laboratory for critically reading the manuscript and helpful discussions. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = feb,
day = "8",
doi = "10.1016/j.cell.2017.12.033",
language = "English (US)",
volume = "172",
pages = "784--796.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}