Hogan, Simon PMishra, AnilBrandt, EricFoster, Paul SRothenberg, Marc E2015-12-130027-8424http://hdl.handle.net/1885/88913Despite marked advances in the understanding of allergic responses, the mechanisms regulating gastrointestinal allergy are not very well understood. We have developed a model of antigen-induced eosinophil-associated gastrointestinal allergy and characterized the role of eotaxin and IL-5. Challenge of allergen-sensitized mice with oral allergen, in the form of enteric-coated beads, resulted in marked allergen-specific IgG1 and IgE, Th2-type (IL-4 and IL-5) cytokine production, and eosinophil accumulation in the blood and small intestine. In the genetic absence of eotaxin, a chemokine constitutively expressed in the gastrointestinal tract, eosinophil recruitment into the small intestine was ablated, and these mice developed enhanced eosinophil accumulation in the blood compared with wild-type mice. Interestingly, in the absence of IL-5, allergen challenge promoted partial eosinophil accumulation into the small intestine and a decline in circulating eosinophil levels. Collectively, these results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5, and provides a molecular mechanism to explain the dichotomy between peripheral blood and tissue eosinophilia. Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract.Keywords: allergen; chemokine receptor CCR3; eotaxin; gamma interferon; immunoglobulin E; immunoglobulin G1; interleukin 4; interleukin 5; major basic protein; allergy; animal cell; animal experiment; animal model; animal tissue; article; controlled study; cytokine200010.1073/pnas.97.12.66812015-12-12