The Il9 CNS-25 regulatory element controls mast cell and basophil IL-9 production

Amina Abdul Qayum, Byunghee Koh, Rebecca K. Martin, Blake T. Kenworthy, Rakshin Kharwadkar, Yongyao Fu, Wenting Wu, Daniel H. Conrad, Mark H. Kaplan

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1111-1121
Number of pages11
JournalJournal of Immunology
Volume203
Issue number5
DOIs
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Qayum, 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. Journal of Immunology, 203(5), 1111-1121. https://doi.org/10.4049/jimmunol.1900272