Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

Derek K Chu, Rodrigo Jimenez-Saiz, Christopher P Verschoor, Tina D Walker, Susanna Goncharova, Alba Llop-Guevara, Pamela Shen, Melissa E Gordon, Nicole G Barra, Jennifer D Bassett, Joshua Kong, Ramzi Fattouh, Kathy D McCoy, Dawn M Bowdish, Jonas Erjefält, Oliver Pabst, Alison A Humbles, Roland Kolbeck, Susan Waserman, Manel Jordana

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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.
Original languageEnglish
Pages (from-to)1657-1672
JournalJournal of Experimental Medicine
Volume211
Issue number8
DOIs
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Immunology in the medical area

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