Paneth cells regulate allergic sensitization in the gastrointestinal tract

Abstract

Abstract The gut immune homeostasis plays a major role in controlling sensitization to food allergens and the development of allergic responses in the gastrointestinal tract, but also to skin or lung. Epithelial cells sensing of commensal microbes is crucial for the maturation of the gut immune system and antibiotic treatment during early life is believed to have contributed to the increased incidence of food allergy. Paneth cells secrete antimicrobial products in the crypts of the small intestine, but their role in food allergic remains elusive. We found that SOX9ΔIEC mice, which lack of Paneth cells, display dysbiosis with increased microbial diversity and the presence of a large number of unclassified bacterial species. Upon oral sensitization with OVA as a model of food antigen in the presence of cholera toxin, SOX9ΔIEC mice developed similar levels of allergen-specific serum IgA and IgG responses to control wild-type mice with the exception of IgG3 responses, which were elevated in SOX9ΔIEC mice. Interestingly, SOX9ΔIEC mice exhibited significantly increased allergen-specific serum IgE responses, and exacerbated signs of allergic responses (i.e., swelling, hypothermia, impairment of lung functions) after nasal allergen challenge. Transplantation of fecal materials from SOX9ΔIEC mice was able to transfer the hyper-allergenic phenotype to control wild-type mice. Ongoing studies are assessing the metabolites present in the intestinal lumen of SOX9ΔIEC mice and their effect on intestinal epithelial cells and myeloid cells to elucidate the mechanisms by which impaired or defective anti-microbial functions of Paneth cells regulate allergic sensitization of the GI tract.