Prophylactic Peanut Allergen Ara h 6 Sublingual Immunotherapy Drives Expansion of FoxP3 +Helios− Regulatory T Cells in the Absence of Allergen-Specific IgA

Abstract

Insights into the underlying immunological mechanisms of prophylactic sublingual immunotherapy (SLIT) may support the development of new strategies for improved prevention and treatment of food allergy. Here, we investigated the humoral, regulatory and sublingual tissue immune response to prophylactic SLIT administration of a single purified peanut allergen in Brown Norway (BN) rats. BN rats received daily sublingual administration of peanut allergen Ara h 6 for three weeks. Suppression of sensitisation was evaluated by subsequent intraperitoneal administration of Ara h 6. Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c levels were measured in serum. The frequency of regulatory T (Treg) cells was analysed using flow cytometry. The sublingual tissue response to Ara h 6 was analysed by transcriptional profiling using mRNA-sequencing. Ara h 6 SLIT protected rats from subsequent sensitisation without inducing a detectable humoral immune response (Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c) in serum. SLIT furthermore promoted the relative expansion of induced Helios⁻ Treg cells within the conventional CD4⁺CD25⁺FoxP3⁺ Treg population in sublingual draining lymph nodes and blood. In conclusion, prophylactic Ara h 6 SLIT drives the relative expansion of induced Helios⁻ Treg cells in the absence of Ara h 6-specific IgA highlighting a potential novel IgA-independent Treg-related immune response at the sublingual mucosal site.