Basophils function as initiators rather than effectors in IgE-mediated chronic allergic inflammation, independently of T cells and mast cells (38.6)

Abstract

Abstract Basophils have often been considered as minor and possibly redundant “circulating mast cells”. We recently demonstrated that basophils play a pivotal role in the development of IgE-mediated chronic allergic inflammation (IgE-CAI), independently of T cells and mast cells. A single subcutaneous injection of multivalent antigens elicited not only immediate- and late-phase ear swelling but also delayed-onset ear swelling with massive eosinophil infiltration in mice sensitized with antigen-specific IgE. Here, we show that basophils function as initiators of the recruitment of eosinophils and neutrophils rather than effectors of inflammation in IgE-CAI. Even though basophils accounted for only 1–2% of the infiltrating cells in the skin legions, treatment of the IgE-sensitized mice with a newly-developed basophil-depleting mAb during the progression of IgE-CAI resulted in suppression of delayed-onset ear swelling with drastic reduction in numbers of not only basophils but also eosinophils and neutrophils infiltrating in the skin legions. Upon activation with IgE and corresponding antigens in vitro, basophils secreted soluble factors that stimulated skin adherent cells to produce soluble factors capable of attracting eosinophils and neutrophils. These findings indicate a novel mechanism of development of chronic allergic inflammation that is initiated and amplified by basophils.