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J Exp Med ; 211(8): 1657-72, 2014 Jul 28.
Article in English | MEDLINE | ID: mdl-25071163

ABSTRACT

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.


Subject(s)
Adaptive Immunity/immunology , Dendritic Cells/immunology , Eosinophils/immunology , Gastrointestinal Tract/cytology , Th2 Cells/immunology , Adaptive Immunity/drug effects , Animals , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , Antigens, CD/metabolism , CD11c Antigen/metabolism , Cell Degranulation/drug effects , Cell Movement/drug effects , Cross-Priming/drug effects , Cross-Priming/immunology , Dendritic Cells/drug effects , Eosinophils/ultrastructure , Erythropoietin/pharmacology , Humans , Immunization , Integrin alpha Chains/metabolism , Interleukin-4/biosynthesis , Mice , Th2 Cells/drug effects
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