Characterizing the regulatory role of diacylglycerol acyltransferase 2 (DGAT2) in IgE-activated mast cells 4362

Abstract Description Mast cells are immune sentinels recognized for their role in allergic inflammation. Allergen-induced FcεRI activation initiates a biphasic response characterized by the rapid degranulation of preformed mediators and the delayed release of cytokines and chemokines. Triacylglycerols (TAG) serve as a source of energy required for cellular functions. Diacylglycerol O-acyltransferase 2 (DGAT2) is an enzyme responsible for the esterification of fatty acids to glycerol during TAG synthesis prior to storage or utilization. Currently, the metabolic requirements of mast cell activation are poorly understood. Therefore, we sought to characterize the importance of TAG as an energy source following allergen activation. IgE-sensitized murine mast cells were treated with the DGAT2 inhibitor JNJ DGAT2-A (JNJ) and stimulated with TNP-BSA and SCF. Following activation, degranulation was measured via β-hexosaminidase release, ELISAs were used to determine cytokine/chemokine release and O2 consumption was measured with a O2k-FluorRespiromoter. Here, DGAT2 inhibition reduced mast cell degranulation (p = 0.02). JNJ treatment significantly reduced the release of IL-6 (p = 0.0002), IL-13 (p = 0.002), TNF (p = 0.0002), CCL1 (p = 0.017) and CCL2 (p = 0.024), independent of any changes to O2 consumption. Together, these results highlight the potential regulatory role of DGAT2 activity during allergen-mediated mast cell activation, making it an intriguing therapeutic target to help combat the allergy epidemic. Funding Sources Canadian Foundation for Innovation (CFI), Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant and Alexandar Graham Bell Canadian Graduate Scholarship (CGS-D), Ontario Government, and Brock University Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)