Different airborne particulates trigger distinct immune pathways leading to peanut allergy in a mouse model

Abstract

BackgroundEnvironmental exposure to peanut through non‐oral routes is a risk factor for peanut allergy. Early‐life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model.MethodsC57BL/6J mice were co‐exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut‐specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM‐induced peanut allergy.ResultsAirway co‐exposure to peanut and either UPM‐ or DEP‐induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut‐specific CD4+ Th cells. UPM‐ and DEP‐induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM‐ and DEP‐induced peanut allergy, whereas TLR4 signaling was dispensable. DEP‐induced peanut allergy and Tfh‐cell differentiation depended on IL‐1 but not IL‐33 signaling, whereas neither cytokine alone was necessary for UPM‐mediated sensitization.ConclusionEnvironmental co‐exposure to peanut and PM induces peanut‐specific Tfh cells and peanut allergy in mice.

Allergenicity and Linear Epitope Analysis of Scy p 8, an Allergen from Mud Crab

“…Mice sera were used as the primary antibody in a 1:5 dilution. The immune cell subpopulations and cytokines were subjected to further analysis based on the methods described in the paper . Mouse spleens ( n = 8) and mesenteric lymph nodes (MLNs) ( n = 8) were collected and utilized to prepare single-cell suspensions, which were stained with CD4 BV650 (GK1.5; Biolegend), CD19 PE (1D3; Biolegend), TCR-β APC (H57–597; BD Biosciences), CD25 Alexa Fluor 700 (PC61; Biolegend), Foxp3 BV421 (MF23; BD Biosciences), IL-4 APC (11B11; Biolegend), IFN-γ PE (XMG1.2; Biolegend), and IL-17A PerCP-Cy5.5 (TC11-18H10.1; Biolegend), which were gated and demonstrated by BD FACS Celesta.…”