‘Uncovering mast cell biology within tissue microenvironments’ 4475

Abstract Description Food allergies are among the most prevalent chronic diseases in the United States. Mast cells are pivotal in allergic inflammation, yet their physiological function remains poorly understood. Since tissue architecture is known to control immune cell biology, we hypothesize that mast cells are also influenced by tissue composition. We aim to dissect how tissue components affect mast cell biology. Using a 2.5D gut-specific extracellular matrix (ECM) to mimic tissue structure and composition, we determined in vitro mast cell degranulation and activation in response to IgE. We also compared two distinct mast cell populations, connective and mucosal mast cells. Upon IgE stimulation, gel-cultured mucosal mast cells showed higher IL-6 and lower TNF-α production compared with mast cells cultured in regular tissue plates, while connective tissue mast cells showed no change in cytokine production. However, connective tissue mast cells displayed upregulation of histidine decarboxylase (Hdc) following IgE stimulation and increased early growth response 1 (Egr1) expression when exposed to ECM at baseline. Our data thus far show that ECM components impact mast cell responses to allergens, suggesting that tissue sensing by mast cells affects their function. Future studies will determine the molecular mechanisms underlying ECM sensing and how specifically ECM impacts mast cell responses to allergens and other non-allergic stimuli. Funding Sources Supported by Food Allergy and Science Initiative (FASI). Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)