| First Author | Abdul Qayum A | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 5 | Pages | 1111-1121 |
| PubMed ID | 31350354 | Mgi Jnum | J:278683 |
| Mgi Id | MGI:6357770 | Doi | 10.4049/jimmunol.1900272 |
| Citation | Abdul Qayum A, et al. (2019) The Il9 CNS-25 Regulatory Element Controls Mast Cell and Basophil IL-9 Production. J Immunol 203(5):1111-1121 |
| abstractText | 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. |
