AUTHOR=Kim Eunsoo , Lembert Melanie , Fallata Ghaith M. , Rowe John C. , Martin Tara L. , Satoskar Abhay R. , Reo Nicholas V. , Paliy Oleg , Cormet-Boyaka Estelle , Boyaka Prosper N. TITLE=Intestinal Epithelial Cells Regulate Gut Eotaxin Responses and Severity of Allergy JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01692 DOI=10.3389/fimmu.2018.01692 ISSN=1664-3224 ABSTRACT=

Intestinal epithelial cells (IECs) are known to regulate allergic sensitization. We addressed the role of the intrinsic IKKβ signaling in IECs in the effector phase of allergy following oral allergen challenge and its impact on the severity of responses is poorly. Upon orally sensitization by co-administration of ovalbumin with cholera toxin as adjuvant, wild-type and mice lacking IKKβ in IECs (IKKβΔIEC mice) developed similar levels of serum IgE and allergen-specific secretory IgA in the gut. However, subsequent allergen challenges in the gut promoted allergic lower responses in KKβΔIEC mice. Analysis of cytokines and chemokines in serum and gut tissues after oral allergen challenge revealed impaired eotaxin responses in IKKβΔIEC mice, which correlated with lower frequencies of eosinophils in the gut lamina propria. We also determined that IECs were a major source of eotaxin and that impaired eotaxin production was due to the lack of IKKβ signaling in IECs. Oral administration of CCL11 to IKKβΔIEC mice during oral allergen challenge enhanced allergic responses to levels in wild-type mice, confirming the role of IEC-derived eotaxin as regulator of the effector phase of allergy following allergen challenge. Our results identified targeting IEC-derived eotaxin as potential strategy to limit the severity of allergic responses to food antigens.