P040 Direct and cooperative activation of human mast cells by IL-33 and IgE

Abstract

Introduction Mast cells mediate allergic responses predominantly by recognizing IgE-bound antigens however they are also activated by endogenous factors. IL-33 is an IL-1-related cytokine expressed abundantly within mucosal tissues that are in close contact with resident mast cells. IL-33 has been shown by us and other groups to act directly on mast cells through its receptor ST2. In this study, we further characterized how IL-33 activates mast cells directly and how it acts synergistically with IgE to modify a variety of allergic cell responses. Methods Mast cells were obtained from differentiated human blood precursors. ST2 expression was measured by flow cytometry and real time PCR. Cytokines, chemokines and histamine was measured using standard assays. Gene expression was also evaluated by microarray hybridization. Results ST2 was expressed on both mouse and human mast cells but can only be demonstrated easily by flow cytometry on mouse mast cells. IL-33 was able to directly induce the release of several cytokines, including IL-5, IL-6, IL-13 and GM-CSF and also synergistically enhanced cytokine and chemokine release induced by IgE receptor activation. Moreover, in the presence of IL-33, a larger fraction of cultured mast cells exhibited a degranulation phenotype and released three times the amount of histamine as that induced by IgE activation alone. Finally, we used microarray analysis to further characterize the gene expression profile of human mast cells activated in different ways, including by IgE signaling or IL-33 signaling. Conclusion These results add to previous findings that IL-33 can activate a variety of mast cell responses, either in the presence or absence of allergen. IL-33 may thus represent an endogenous activating signal from adjacent tissue cells to amplify and modify mast cell responses.