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Immunity. 2015 Nov 17;43(5):1011-21. doi: 10.1016/j.immuni.2015.10.016.

A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes.

Author information

1
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria.
3
National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892, USA.
4
Center for Immunology and Inflammatory Diseases, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
5
Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, 72076 Tübingen, Germany.
6
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
7
Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
8
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: michael.rosenblum@ucsf.edu.

Abstract

The skin is a site of constant dialog between the immune system and commensal bacteria. However, the molecular mechanisms that allow us to tolerate the presence of skin commensals without eliciting destructive inflammation are unknown. Using a model system to study the antigen-specific response to S. epidermidis, we demonstrated that skin colonization during a defined period of neonatal life was required for establishing immune tolerance to commensal microbes. This crucial window was characterized by an abrupt influx of highly activated regulatory T (Treg) cells into neonatal skin. Selective inhibition of this Treg cell wave completely abrogated tolerance. Thus, the host-commensal relationship in the skin relied on a unique Treg cell population that mediated tolerance to bacterial antigens during a defined developmental window. This suggests that the cutaneous microbiome composition in neonatal life is crucial in shaping adaptive immune responses to commensals, and disrupting these interactions might have enduring health implications.

PMID:
26588783
PMCID:
PMC4654993
DOI:
10.1016/j.immuni.2015.10.016
[Indexed for MEDLINE]
Free PMC Article

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