Activated plasmacytoid dendritic cells regulate type 2 innate lymphoid cell-mediated airway hyperreactivity.

Autor: Maazi H; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif., Banie H; Janssen Research and Development, San Diego, Calif., Aleman Muench GR; Janssen Research and Development, San Diego, Calif., Patel N; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif., Wang B; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif., Sankaranarayanan I; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif., Bhargava V; Janssen Research and Development, Spring House, Philadelphia, Pa., Sato T; Janssen Research and Development, Spring House, Philadelphia, Pa., Lewis G; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif; Janssen Research and Development, San Diego, Calif., Cesaroni M; Janssen Research and Development, Spring House, Philadelphia, Pa., Karras J; Janssen Research and Development, San Diego, Calif., Das A; Janssen Research and Development, Spring House, Philadelphia, Pa., Soroosh P; Janssen Research and Development, San Diego, Calif., Akbari O; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif. Electronic address: akbari@usc.edu.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2018 Mar; Vol. 141 (3), pp. 893-905.e6. Date of Electronic Publication: 2017 Jun 01.
DOI: 10.1016/j.jaci.2017.04.043
Abstrakt: Background: Allergic asthma is a prevalent inflammatory disease of the airways caused by dysregulated immune balance in the lungs with incompletely understood pathogenesis. The recently identified type 2 innate lymphoid cells (ILC2s) play significant roles in the pathogenesis of asthma. Although ILC2-activating factors have been identified, the mechanisms that suppress ILC2s remain largely unknown. Plasmacytoid dendritic cells (pDCs) are important in antiviral immunity and in maintaining tolerance to inert antigens.
Objective: We sought to address the role of pDCs in regulating ILC2 function and ILC2-mediated airway hyperreactivity (AHR) and lung inflammation.
Methods: We used several murine models, including BDCA-2-diphtheria toxin receptor (DTR) transgenic and IFN-α receptor 1-deficient mice, as well as purified primary ILC2s, to reach our objective. We extended and validated our findings to human ILC2s.
Results: We show that activation of pDCs through Toll-like receptor 7/8 suppresses ILC2-mediated AHR and airway inflammation and that depletion of pDCs reverses this suppression. We further show that pDCs suppress cytokine production and the proliferation rate while increasing the apoptosis rate of ILC2s through IFN-α production. Transcriptomic analysis of both human and murine ILC2s confirms the activation of regulatory pathways in ILC2s by IFN-α.
Conclusion: Activation of pDCs alleviates AHR and airway inflammation by suppressing ILC2 function and survival. Our findings reveal a novel regulatory pathway in ILC2-mediated pulmonary inflammation with important clinical implications.
(Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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