Cell intrinsic role of mast cell steroidogenesis

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B638
Abstract ID: 7493

Presenting Author:
Jhuma Pramanik , Post doc at Univ. of Cambridge

Abstract:

Mast cells are involved in physiological functions such as vasodilation, vascular homeostasis, innate and adaptive immunity, angiogenesis, and venom detoxification. In contrast, dysregulation or uncontrolled regulation of mast cell function is critical in pathogenesis, including anaphylaxis, allergies, asthma, gastrointestinal disorders, and cancer. Little is known about the negative regulatory mechanisms of fine-tuning the mast cell function. In this study, we discovered that mast cells synthesise and secrete immunoregulatory steroid pregnenolone. Undertaking an integrated omics approach, we reveal the cell intrinsic role of mast cell steroidogenesis. We genetically deleted Cyp11a1, the enzyme that catalyses the first and rate-limiting step of steroidogenesis, and compared the transcriptome, proteome and steroidome of bone marrow and peritoneal cavity derived mast cells, before and after IgE dependent degranulation. From our observations, we concluded that mast cell mediated steroidogenesis is required as a negative regulatory mechanism to keep mast cell function under control. In the preclinical mice model of cancer, mast cell steroidogenesis suppresses anti-tumour immunity and promotes carcinogenesis, which can be targeted pharmacologically by inhibiting the pathway.