Assessing The Role of the NLRP3 Inflammasome In Pollutant-Mediated Peanut Allergy

Peanut allergy is a potentially life-threatening disease affecting approximately 5.9 million children in the United States(1). The severity of peanut allergies necessitates a comprehensive understanding of its intricacies, especially in the context of environmental exposures that pose a risk to its development. Exposure to peanut in the lungs is known to increase levels of the cytokines IL-1α and IL-1β, leading to the activation of Tfh cells and eventually the development of allergy (2). A recent study by the Moran lab revealed that diesel exhaust particles (DEP) and urban particulate matter (UPM) promote allergic sensitization to peanut through different pathways following airway co-exposure (3). Airway exposure to DEP and UPM induced the innate cytokines IL-1α and/or IL-1β, and DEP-mediated allergic sensitization was dependent on the IL-1 receptor (3). This discovery, along with others (2), has sparked increased interest in the activation of IL-1 typically accomplished by the NLRP3-dependent proteasome as an initiating factor in allergic sensitization. This project aims to better understand the mechanisms behind allergic sensitization driven by DEP and UPM, specifically looking at the role of the NLRP3 inflammasome. To determine whether DEP or UPM-mediated pathways require NLRP3 for sensitization, wild-type and Nlrp3-/- mice will be treated using the Moran lab’s airway mouse model of peanut allergy. This research will contribute vital insights into the mechanisms that underlie the development of peanut allergy by addressing the involvement of NLRP3 in pollutant-mediated allergic sensitization. 1. Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128(1):e9-17. doi:10.1542/peds.2011-0204 2. Dolence JJ, Kobayashi T, Iijima K, et al. Airway exposure initiates peanut allergy by involving the IL-1 pathway and T follicular helper cells in mice. J Allergy Clin Immunol. 2018;142(4):1144-1158.e8. doi:10.1016/j.jaci.2017.11.020 3. Immormino RM, Smeekens JM, Mathai PI, et al. Different airborne particulates trigger distinct immune pathways leading to peanut allergy in a mouse model. Allergy. Published online October 7, 2023. doi:10.1111/all.15908