Fachbereich Veterinärmedizin



    Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines (2012)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Hepworth, Matthew R
    Daniłowicz-Luebert, Emilia
    Rausch, Sebastian
    Metz, Martin
    Klotz, Christian
    Maurer, Marcus
    Hartmann, Susanne
    Proceedings of the National Academy of Sciences of the United States of America; 109(17) — S. 6644–6649
    ISSN: 0027-8424
    DOI: 10.1073/pnas.1112268109
    Pubmed: 22493240
    Institut für Immunologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
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    Abstract / Zusammenfassung

    Mast cells (MCs) are potent inflammatory cells that are distributed throughout mucosal barrier tissues and respond rapidly to pathogenic stimuli. During helminth infections, MCs play an important role as late-stage effectors. However, it is currently unknown whether MCs contribute to the early innate events that determine the priming of adaptive immunity. MC-deficient mouse strains and mice treated with the MC stabilizing agent cromolyn sodium had dramatically reduced Th2 priming and type 2 cytokine production and harbored increased parasite burdens following infection with gastrointestinal helminths (Heligmosomoides polygyrus bakeri and Trichuris muris). In addition, early production of the tissue-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) was significantly diminished in MC-deficient mice and resulted in decreased numbers of infection-elicited IL-25-dependent (Lin(-)CD45(-))CD34(+)Sca-1(+) progenitors, which produced type 2 cytokines and could be differentiated into mast cells ex vivo. Finally, repair of MC deficiency increased production of IL-25, IL-33, and TSLP, restored progenitor cell numbers and Th2 priming, and reduced parasite burden. Our data reveal an innate IgE-independent role for MCs in orchestrating type 2 immune responses via the regulation of IL-25, IL-33, and TSLP.