Qayum, Amina AbdulKoh, ByungheeMartin, Rebecca K.Kenworthy, Blake T.Kharwadkar, RakshinFu, YongyaoWu, WentingConrad, Daniel H.Kaplan, Mark H.2021-05-292021-05-292019-09-01Qayum, A. A., Koh, B., Martin, R. K., Kenworthy, B. T., Kharwadkar, R., Fu, Y., Wu, W., Conrad, D. H., & Kaplan, M. H. (2019). The Il9 CNS-25 Regulatory Element Controls Mast Cell and Basophil IL-9 Production. The Journal of Immunology, 203(5), 1111–1121. https://doi.org/10.4049/jimmunol.19002720022-1767, 1550-6606https://hdl.handle.net/1805/26081Interleukin 9 (IL-9) is an important mediator of allergic disease that is critical for mast cell driven diseases. IL-9 is produced by many cell types including T cells, basophils, and mast cells. Yet, how IL-9 is regulated in mast cells or basophils is not well characterized. In this report we tested the effects of deficiency of a mouse Il9 gene regulatory element (Il9 CNS-25) in these cells in vivo and in vitro. In mast cells stimulated with IL-3 and IL-33, the Il9 CNS-25 enhancer is a potent regulator of mast cell Il9 gene transcription and epigenetic modification at the Il9 locus. Our data show preferential binding of STAT5 and GATA1 to CNS-25 over the Il9 promoter in mast cells, and that T cells and mast cells have differing requirements for the induction of IL-9 production. Il9 CNS-25 is required for IL-9 production from T cells, basophils, and mast cells in a food allergy model, and deficiency in IL-9 expression results in decreased mast cell expansion. In a Nippostrongylus brasiliensis infection model we observed a similar decrease in mast cell accumulation. Although decreased mast cells correlated with higher parasite egg burden and delayed clearance in vivo, T cell-deficiency in IL-9 also likely contributes to the phenotype. Thus, our data demonstrate IL-9 production in mast cells and basophils in vivo requires Il9 CNS-25, and that Il9 CNS-25-dependent IL-9 production is required for mast cell expansion during allergic intestinal inflammation.en-USBasophilsGenes RegulatorInterleukin-9Mast CellsArticle