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 Kaplan

Research output: Contribution to journalArticle

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

Fingerprint

Interleukin-9
Basophils
Mast Cells
T-Lymphocytes
Nippostrongylus
Mastocytosis
Food Hypersensitivity
Interleukin-3
Regulator Genes
Epigenomics
Ovum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Qayum, A. A., Koh, B., Martin, R. K., Kenworthy, B. T., Kharwadkar, R., Fu, Y., ... Kaplan, M. (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

The Il9 CNS-25 regulatory element controls mast cell and basophil IL-9 production. / Qayum, Amina Abdul; Koh, Byunghee; Martin, Rebecca K.; Kenworthy, Blake T.; Kharwadkar, Rakshin; Fu, Yongyao; Wu, Wenting; Conrad, Daniel H.; Kaplan, Mark.

In: Journal of Immunology, Vol. 203, No. 5, 01.09.2019, p. 1111-1121.

Research output: Contribution to journalArticle

Qayum, AA, Koh, B, Martin, RK, Kenworthy, BT, Kharwadkar, R, Fu, Y, Wu, W, Conrad, DH & Kaplan, M 2019, 'The Il9 CNS-25 regulatory element controls mast cell and basophil IL-9 production', Journal of Immunology, vol. 203, no. 5, pp. 1111-1121. https://doi.org/10.4049/jimmunol.1900272
Qayum AA, Koh B, Martin RK, Kenworthy BT, Kharwadkar R, Fu Y et al. The Il9 CNS-25 regulatory element controls mast cell and basophil IL-9 production. Journal of Immunology. 2019 Sep 1;203(5):1111-1121. https://doi.org/10.4049/jimmunol.1900272
Qayum, Amina Abdul ; Koh, Byunghee ; Martin, Rebecca K. ; Kenworthy, Blake T. ; Kharwadkar, Rakshin ; Fu, Yongyao ; Wu, Wenting ; Conrad, Daniel H. ; Kaplan, Mark. / The Il9 CNS-25 regulatory element controls mast cell and basophil IL-9 production. In: Journal of Immunology. 2019 ; Vol. 203, No. 5. pp. 1111-1121.
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