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Proc Natl Acad Sci U S A. 2019 May 28;116(22):10917-10926. doi: 10.1073/pnas.1818256116. Epub 2019 May 14.

Clonal Vγ6+Vδ4+ T cells promote IL-17-mediated immunity against Staphylococcus aureus skin infection.

Author information

1
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
2
Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817.
3
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
4
The Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
5
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
6
Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502.
7
Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA 90502.
8
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.
9
Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502.
10
Department of Biomedical Engineering, University of California, Davis, CA 95616.
11
Cytokines and Immunity Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
12
Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
13
Department of Immunology and Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80206.
14
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231; lloydmiller@jhmi.edu.
15
Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
16
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
17
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.

Abstract

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4 However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

KEYWORDS:

IL-17; Staphylococcus aureus; T cells; neutrophils; skin

PMID:
31088972
PMCID:
PMC6561199
[Available on 2019-11-14]
DOI:
10.1073/pnas.1818256116

Conflict of interest statement

Conflict of interest statement: M.R.Y. is a cofounder of NovaDigm Therapeutics, which is developing novel vaccines and immunotherapeutics for infectious diseases, including S. aureus. L.S.M. has received grant support for work unrelated to the work reported in this manuscript from AstraZeneca, Pfizer, Regeneron Pharmaceuticals, Moderna Therapeutics, and Boehringer Ingelheim, is on the scientific advisory board for Integrated Biotherapeutics, and is a shareholder of Noveome Biotherapeutics, which are each developing vaccines and therapeutics against S. aureus and other pathogens.

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