Allergen-encapsulating Nanoparticles Reprogram Pathogenic Allergen-Specific Th2 Cells to Suppress Food Allergy.

Food allergy is a prevalent and potentially deadly disease caused by inadvertent sensitization to benign food antigens. Pathogenic Th2 cells are a major driver for disease, and allergen-specific immunotherapies (AIT) aim to increase the allergen threshold required to elicit severe allergic symptoms. However, the majority of AIT approaches require lengthy treatments and convey transient disease suppression, likely due to insufficient targeting of pathogenic Th2 responses. Here, we investigate the ability of allergen-encapsulating nanoparticles to directly suppress pathogenic Th2 responses and reactivity in a mouse model of food allergy. NPs associate with pro-tolerogenic antigen presenting cells, provoking the accumulation of antigen-specific, functionally suppressive regulatory T cells in the small intestine lamina propria. We report that 2 intravenous doses of allergen encapsulated in poly(lactide-co-glycolide) nanoparticles (NPs) significantly reduces oral food challenge (OFC)-induced anaphylaxis. Importantly, we demonstrate that NP treatment alters the fates of pathogenic allergen-specific Th2 cells, reprogramming these cells towards CD25+ FoxP3+ regulatory and CD73+ FR4+ anergic phenotypes. We also demonstrate NP-mediated reductions in the frequency of effector cells in the gut and mast cell degranulation following OFC. These studies reveal mechanisms by which an allergen-encapsulating NP therapy and, more broadly, allergen-specific immunotherapies, can rapidly attenuate allergic responses by targeting pathogenic Th2 cells. This article is protected by copyright. All rights reserved.