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Jun-Xia Wang, Shinjiro Kaieda, Peter Nigrovic, IL-33/ST2 promotes tissue mastocytosis under conditions of inflammation (CCR3P.219), The Journal of Immunology, Volume 192, Issue Supplement_1, May 2014, Page 115.16, https://doi.org/10.4049/jimmunol.192.Supp.115.16
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Abstract
Mast cells (MC) are potent innate immune cells that accumulate in chronically inflamed tissues, where they have been implicated in multiple allergic and inflammatory diseases. MC express the IL-33 receptor ST2, and this new member of the IL-1 cytokine family is recognized as an important pathway both for direct MC activation and for priming MC to respond to other pro-inflammatory signals. However, IL-33 has no known role in tissue mastocytosis. Using primary MC cultured from human skin, we found that IL-33 did not alter MC proliferation but instead protected MC from apoptosis, principally through upregulation of the anti-apoptotic molecule BCLXL. Murine bone marrow-derived MC demonstrated a similar response to IL-33, dependent entirely upon ST2, allowing us to test the role of this biology in vivo. Mice lacking ST2 exhibited fewer peritoneal MC as well as reduced accumulation of MC in inflamed arthritic joints and helminth-infected intestine. Upon engraftment into the peritoneum, WT MC exhibited a clear, IL-33-mediated survival advantage over ST2-deficient MC, in particular after thioglycollate-induced peritonitis. Together, these data reveal a novel, cell-intrinsic role for the IL-33/ST2 axis in tissue mastocytosis, especially under conditions of local inflammation.