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Cell. 2018 Feb 8;172(4):784-796.e18. doi: 10.1016/j.cell.2017.12.033. Epub 2018 Jan 18.

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

Author information

1
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
2
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, NHGRI, NIH, Bethesda, MD 20892, USA; Department of Bioinformatics, Boston University, Boston, MA 02215, USA.
3
Molecular Immunology and Inflammation Branch, NIAMS, NIH, Bethesda, MD 20892, USA.
4
Cancer and Inflammation Program, NCI, NIH, Bethesda, MD 20892, USA.
5
Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
6
Biological Imaging, Research Technology Branch, NIAID, NIH, Bethesda, MD 20892, USA.
7
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA; NIAID Microbiome Program, NIH, Bethesda, MD 20892, USA.
8
Immunology Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, MD 20892, USA.
9
Molecular Genetics Section, NIAID, NIH, Bethesda, MD 20892, USA.
10
Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611, USA.
11
Barrier Immunity Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
12
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.

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.

KEYWORDS:

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

PMID:
29358051
PMCID:
PMC6034182
DOI:
10.1016/j.cell.2017.12.033
[Indexed for MEDLINE]
Free PMC Article

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