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

Jonathan L. Linehan, Oliver J. Harrison, Seong Ji Han, Allyson L. Byrd, Ivan Vujkovic-Cvijin, Alejandro V. Villarino, Shurjo K. Sen, Jahangheer Shaik, Margery Smelkinson, Samira Tamoutounour, Nicholas Collins, Nicolas Bouladoux, Amiran Dzutsev, Stephan P. Rosshart, Jesse H. Arbuckle, Chyung Ru Wang, Thomas M. Kristie, Barbara Rehermann, Giorgio Trinchieri, Jason M. BrenchleyJohn J. O'Shea, Yasmine Belkaid*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)784-796.e18
JournalCell
Volume172
Issue number4
DOIs
StatePublished - Feb 8 2018

Keywords

  • H2-M3
  • MHCIb
  • Staphylococcus epidermidis
  • microbiota
  • non-classical MHC class I
  • skin immunity
  • tissue repair

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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