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HB-EGF Synthesized by CD4 T Cells Modulates Allergic Airway Eosinophilia by Regulating IL-5 Synthesis.

Abstract
CD4 T cells express the epidermal growth factor (EGF) receptor ligand, heparin-binding EGF (HB-EGF), with no defined immuno-pathophysiological function. Therefore, we wished to elucidate the function of HB-EGF synthesized by CD4 T cells in the context of allergic pulmonary inflammation and the asthma surrogate, airway hyperresponsiveness, in a murine acute model of asthma. In this study, we show how knocking out HB-EGF expression in CD4 T cells in vivo attenuates IL-5 synthesis in the lung that is accompanied by diminished eosinophilic inflammation and airway hyperresponsiveness. HB-EGF coimmunoprecipitates with the transcriptional repressor B cell lymphoma 6 (Bcl-6) in CD4 T cells. Knocking out HB-EGF in CD4 T cells resulted in increased Bcl-6 binding to the IL-5 gene and decreased IL-5 mRNA expression. Thus, these findings suggest an immunoregulatory function for intrinsic HB-EGF expressed by CD4 T cells in TH2 inflammation and airway dysfunction by modulating IL-5 expression via binding to and inhibiting the repressive function of Bcl-6.
AuthorsSoroor Farahnak, Leora Simon, Toby K McGovern, Michael Chen, Niusha Khazaei, James G Martin
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 203 Issue 1 Pg. 39-47 (07 01 2019) ISSN: 1550-6606 [Electronic] United States
PMID31127030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 by The American Association of Immunologists, Inc.
Chemical References
  • CD4 Antigens
  • Heparin-binding EGF-like Growth Factor
  • Interleukin-5
  • Proto-Oncogene Proteins c-bcl-6
Topics
  • Animals
  • Asthma (immunology)
  • CD4 Antigens (metabolism)
  • Disease Models, Animal
  • Eosinophilia (immunology)
  • Gene Expression Regulation
  • Heparin-binding EGF-like Growth Factor (genetics, metabolism)
  • Humans
  • Interleukin-5 (genetics, metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-6 (genetics, metabolism)
  • Respiratory Hypersensitivity (immunology)
  • Th2 Cells (immunology)

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