Protective role of epithelial TRPV4 in the pathogenesis of OVA-induced food allergy in mice

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  • OVA誘発マウス食物アレルギーの病態における温度感受性TRPV4の役割

Abstract

<p>Intestinal epithelial barrier plays a crucial role in the maintenance of gastrointestinal integrity by limiting penetration of luminal bacteria and dietary allergens. TRPV4 is a non-selective cation channel that responds to mechanical, thermal, chemical stimuli, and various endogenous ligands, such as arachidonic acid metabolites. We previously reported that TRPV4 upregulated in vascular endothelia increased vascular permeability during colonic inflammation. The present study investigated the role of TRPV4 in the pathogenesis of ovalbumin (OVA)-induced food allergy in mice. TRPV4-immunoreactivities were detected in epithelial cells but not vascular endothelial cells in the colon of normal and OVA-treated wild-type (WT) mice. TRPV4 knockout (TRPV4KO) mice showed more severe systemic symptoms consist of body weight loss, pruritus, itching, and diarrhea, accompanied by serum OVA-specific IgE levels in OVA-induced food allergy than WT mice. However, colonic permeability in normal and OVA-induced food allergy was not affected by TRPV4KO. Furthermore, TRPV4KO upregulated CD11c-, CD117-, occludin-, Ki67-positive cells, and goblet cells in the colonic mucosa of OVA-induced food allergy compared with WT. These results suggest that epithelial TRPV4 plays a protective role in food allergy via regulation of epithelium-immune interaction.</p>

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