Antigen-Specific Gut Inflammation and Systemic Immune Responses Induced by Prolonging Wheat Gluten Sensitization in BALB/c Murine Model.

Gluten-related diseases such as wheat allergy, celiac
disease, and gluten intolerance are widespread around the globe to
genetically predisposed individuals. The present study aims to
develop a wheat-gluten induced BALB/c murine model for
addressing wheat-gluten related disorders by sensitizing the wheat
gluten through the route of intraperitoneal and oral challenge in
prolonged days. During the sensitization, the sera were collected for
specific antigliadin antibodies response and proinflammatory
markers quantification. Ex vivo primary cells and organs were
collected for subsequent analysis of inflammatory profile.
Prolonging sensitization of gluten can moderate the antigen-specific
inflammatory markers such as IL-1β, IL-4, IL-15, IL-6, IFN-γ and
TNF-α levels in mice sera. However, ex vivo primary cells of
splenocytes (SPLs) and intestinal epithelial lymphocytes (IELs) significantly increased the IL-6, IL-15, IL-1β, and IL-4 levels in G
+ (gliadin and gluten) treated cells. Histopathology staining of jejunum sections indicates enterocyte degeneration in the apical
part of villi and damage of tight junctions in G+ (gliadin and gluten) sensitized murine model. Immunohistochemistry of
embedded jejunum sections showed significant expression of positive cells of IL-15, tTG and IL-4 in G+ sensitized murine
model. In contrast, all markers of gluten-related disorders are expressed exclusively such as tTG, ZO-1, IL-15, IL-6, IL-4, and
intestinal inflammation was mediated by iNOS, COX-2, TLR-4 and NF-kBp50 signaling mechanism in G+ sensitized mice.