Allergic inflammation is initiated by IL-33–dependent crosstalk between mast cells and basophils

Autoři: Chia-Lin Hsu aff001;  Krishan D. Chhiba aff001;  Rebecca Krier-Burris aff001;  Shweta Hosakoppal aff001;  Sergejs Berdnikovs aff001;  Mendy L. Miller aff001;  Paul J. Bryce aff001
Působiště autorů: Division of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America aff001
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


IgE-primed mast cells in peripheral tissues, including the skin, lung, and intestine, are key initiators of allergen-triggered edema and inflammation. Particularly in severe forms of allergy, this inflammation becomes strongly neutrophil dominated, and yet how mast cells coordinate this type of response is unknown. We and others have reported that activated mast cells––a hematopoietic cell type––can produce IL-33, a cytokine known to participate in allergic responses but generally considered as being of epithelial origin and driving Type 2 immune responses (e.g., ILC2 and eosinophil activation). Using models of skin anaphylaxis, our data reveal that mast cell-derived IL-33 also initiates neutrophilic inflammation. We demonstrate a cellular crosstalk mechanism whereby activated mast cells crosstalk to IL-33 receptor–bearing basophils, driving these basophils to adopt a unique response signature rich in neutrophil-associated molecules. We further establish that basophil expression of CXCL1 is necessary for IgE-driven neutrophilic inflammation. Our findings thus unearth a new mechanism by which mast cells initiate local inflammation after antigen triggering and might explain the complex inflammatory phenotypes observed in severe allergic diseases. Moreover, our findings (i) establish a functional link from IL-33 to neutrophilic inflammation that extends IL-33–mediated biology well beyond that of Type 2 immunity, and (ii) demonstrate the functional importance of hematopoietic cell–derived IL-33 in allergic pathogenesis.

Klíčová slova:

Basophils – Cytokines – Ears – Flow cytometry – Inflammation – Inflammatory diseases – Mast cells – Neutrophils


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