Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair.

TitleNon-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair.
Publication TypeJournal Article
Year of Publication2018
AuthorsLinehan, JL, Harrison, OJ, Han, S-J, Byrd, AL, Vujkovic-Cvijin, I, Villarino, AV, Sen, SK, Shaik, J, Smelkinson, M, Tamoutounour, S, Collins, N, Bouladoux, N, Dzutsev, A, Rosshart, SP, Arbuckle, JH, Wang, C-R, Kristie, TM, Rehermann, B, Trinchieri, G, Brenchley, JM, O'Shea, JJ, Belkaid, Y
JournalCell
Volume172
Issue4
Pagination784-796.e18
Date Published2018 02 08
ISSN1097-4172
KeywordsAdaptive Immunity, Animals, Bacteria, Gene Expression Regulation, Histocompatibility Antigens Class I, Mice, Mice, Transgenic, Microbiota, Skin, T-Lymphocytes
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.

DOI10.1016/j.cell.2017.12.033
Alternate JournalCell
PubMed ID29358051
PubMed Central IDPMC6034182
Grant ListR01 AI040310 / AI / NIAID NIH HHS / United States
ZIA AI001115-05 / / Intramural NIH HHS / United States
ZIA AI001115-07 / / Intramural NIH HHS / United States