Induction of Food Allergy in Mice by Allergen Inhalation
Abstract
This proposal tested a hypothesis about food allergy (FA) pathogenesis. Specifically, we hypothesized that: 1) the route of Ag exposure is critical for determining whether FA development is promoted or suppressed, with airway exposure being more likely than enteric exposure to promote FA; 2) inflammatory costimuli promote the induction of FA by inhaled Ags; 3) inhalation of sub-immunogenic quantities of Ag can induce tolerance instead of priming for FA; and 4) Ag inhalation can sensitize for the development of FA to subsequently ingested, cross-reactive Ags. Using a mouse model of FA to eggs, we found evidence that supports the first 2 hypotheses, with the novel and important observation that saturated fats, including those present in egg yolk, act as an inflammatory costimulus by inducing an unfolded protein response that promotes epithelial cell production of cytokines that stimulate allergy. This led to the clinically relevant observation that FDA-approved drugs that inhibit the unfolded protein response, such as metformin, inhibit the FA induction and suppress established FA. However, studies aimed at demonstrating hypothesis 3 were negative and studies aimed at demonstrating hypothesis 4 were inconclusive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2016
- Accession Number
- AD1035018
Entities
People
- Fred Finkelman