Macrophages participate in IL-17-mediated inflammation

Authors

  • Jobert G. Barin,

    1. Training Program in Immunology, Johns Hopkins University School of Medicine, Boltimore, MD, USA
    2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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  • G. Christian Baldeviano,

    1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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  • Monica V. Talor,

    1. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Lei Wu,

    1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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  • SuFey Ong,

    1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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  • Farhan Quader,

    1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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  • Ping Chen,

    1. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Key Laboratory of Viral Heart Diseases, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
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  • Dongfeng Zheng,

    1. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Patrizio Caturegli,

    1. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Noel R. Rose,

    1. Training Program in Immunology, Johns Hopkins University School of Medicine, Boltimore, MD, USA
    2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
    3. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Daniela C̆iháková

    Corresponding author
    1. Department of Pathology, Division of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • JHUSOM, Department of Pathology, 720 Rutland Avenue, Baltimore, MD 21205-2109, USA, Fax: +1-410-614-3548
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Abstract

The involvement of macrophages (MΦs) in Th17-cell responses is still poorly understood. While neutrophils are thought to be the predominant effector of Th17-cell responses, IL-17 is also known to induce myelotropic chemokines and growth factors. Other T-cell-derived cytokines induce non-classical functions, suggesting that IL-17 sigxnaling may similarly elicit unique MΦ functions. Here, we characterized the expression of subunits of the IL-17 receptor on primary murine MΦs from different anatomical compartments. The greatest expression of IL-17 receptors was observed on mucosal Ly6Chi "inflammatory" MΦs. We further observed upregulation of IL-17 receptors in vitro on bone marrow-derived macrophages (BMMΦs) in response to peptidoglycan or CpG oligonucleotide stimuli, and in vivo, upon CFA administration. Macrophages expressing IL-17 receptors were observed infiltrating the hearts of mice with myocarditis, and genetic ablation of IL-17RA altered MΦ recruitment. Treating primary MΦs from a wide variety of different anatomic sources (as well as cell lines) with IL-17A induced the production of unique profiles of cytokines and chemokines, including GM-CSF, IL-3, IL-9, CCL4/MIP-1β and CCL5/RANTES. IL-17A also induced production of IL-12p70; IL-17-signaling-deficient MΦs elicited diminished IFN-γ production by responding DO11.10 CD4+ T cells when used as APCs. These data indicate that MΦs from different anatomic locations direct IL-17-mediated responses.

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