ATP functions as a primary alarmin in allergen-induced type 2 immunity

Abstract

Environmental allergens that interact with the airway epithelium can activate cellular stress pathways that lead to the release of danger signals known as alarmins. The mechanisms of alarmin release are distinct from Damage-Associated Molecular Patterns (DAMPs), which typically escape from cells following loss of plasma membrane integrity. Oxidative stress represents a form of allergen-induced cellular stress that stimulates oxidant-sensing mechanisms coupled to pathways, which facilitate alarmin mobilization and efflux across the plasma membrane. In this review we highlight examples of alarmin release and discuss their role in the initiation of type 2 immunity and allergic airway inflammation. In addition, we discuss the concept of alarmin amplification where "primary" alarmins, which are directly released in response to a specific cellular stress, stimulate additional signaling pathways that lead to secretion of "secondary" alarmins that include pro-inflammatory cytokines, such as IL-33 as well as genomic and mitochondrial DNA that coordinate or amplify type 2 immunity. Accordingly, allergen-evoked cellular stress can elicit a hierarchy of alarmin signaling responses from the airway epithelium that trigger local innate immune reactions, impact adaptive immunity and exacerbate diseases including asthma and other chronic inflammatory conditions that affect airway function.

New biologics for food allergy

“…Epithelial barrier defects such as in atopic dermatitis allow food allergens to penetrate the epithelial barrier and encounter immune cells, which can lead to food sensitization and the development of FA [21]. This sensitization is thought to be mediated by the release of alarmins [also called damage-associated molecular patterns (DAMPs)], such as IL-33, TSLP, and IL-25, which are released by damaged epithelial cells which signal type 2 innate lymphoid cells (ILC2 cells) to promote T H 2 responses that drive allergic reactions [22,23]. In line with their role in sensitization, alarmins have also been reported to be increased in patients with food allergy [24], making them promising targets for the treatment of food allergy.…”