ILC2-derived IL-13 likely promotes development of peanut allergy

Abstract

Abstract Background Peanut (PN) allergies are life-long diseases that cause severe anaphylactic responses to affected individuals. Allergic immune responses are typically mediated by CD4+ T cells producing type 2 cytokines. However, there is little information available regarding the immunological mechanisms that initiate the development of PN allergen-specific T cells and production of PN specific-IgE (PN-IgE). Goal The goal of this study was to elucidate the mechanisms involved in initiation of peanut allergy. Results Naïve BALB/c mice (wt) chronically exposed intranasally (i.n.) to PNf developed PN allergy as demonstrated by increased serum levels of PN-IgE as well as acute anaphylactic response when challenged intraperitoneally with PN extract. Acute i.n. exposure of naïve mice to PNf increased the lung levels of IL-13. By using IL-13eGFP reporter mice, we found that group 2 innate lymphoid cells (ILC2s) produce IL-13 when mice are exposed to PNf. Further, IL-13−/− mice showed significant decrease in the numbers of follicular helper T cells in dLNs and serum levels of PN-IgE relative to wild type (wt) mice. When naïve mice were exposed daily to PNf for 2 days, wt mice showed a significant increase in the numbers of dendritic cells (DCs) in the lung dLN; in contrast, overall dLN cellularity as well as number of DCs was decreased in IL-13−/− mice. Furthermore, there were fewer CD11c+ MHC2+ DCs in dLN of IL-13−/− mice, indicating a role for IL-13 in maturation of DCs. Conclusions Our findings show that airway exposure to PN induces allergy sensitization by mechanisms involving ILC2-derived IL-13 that mediate the migration and maturation of lung DCs to the dLN. The interplay between ILC2s and DCs are likely critical for development of peanut allergy.