The transcription factor Etv5 controls TH17 cell development and allergic airway inflammation

Duy Pham, Sarita Sehra, Xin Sun, Mark Kaplan

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background The differentiation of TH17 cells, which promote pulmonary inflammation, requires the cooperation of a network of transcription factors. Objectives We sought to define the role of Etv5, an Ets-family transcription factor, in TH17 cell development and function. Methods TH17 development was examined in primary mouse T cells wherein Etv5 expression was altered by retroviral transduction, small interfering RNA targeting a specific gene, and mice with a conditional deletion of Etv5 in T cells. The direct function of Etv5 on the Il17 locus was tested with chromatin immunoprecipitation and reporter assays. The house dust mite-induced allergic inflammation model was used to test the requirement for Etv5-dependent T H17 functions in vivo. Results We identify Etv5 as a signal transducer and activator of transcription 3-induced positive regulator of T H17 development. Etv5 controls TH17 differentiation by directly promoting Il17a and Il17f expression. Etv5 recruits histone-modifying enzymes to the Il17a-Il17f locus, resulting in increased active histone marks and decreased repressive histone marks. In a model of allergic airway inflammation, mice with Etv5-deficient T cells have reduced airway inflammation and IL-17A/F production in the lung and bronchoalveolar lavage fluid compared with wild-type mice, without changes in TH2 cytokine production. Conclusions These data define signal transducer and activator of transcription 3-dependent feed-forward control of TH17 cytokine production and a novel role for Etv5 in promoting T cell-dependent airway inflammation.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Th17 Cells
Transcription Factors
Histone Code
Inflammation
T-Lymphocytes
STAT3 Transcription Factor
Bronchoalveolar Lavage Fluid
Proto-Oncogene Proteins c-ets
Cytokines
Pyroglyphidae
Interleukin-17
Chromatin Immunoprecipitation
Histones
Small Interfering RNA
Pneumonia
Enzymes
Genes

Keywords

  • allergic inflammation
  • epigenetic modifications
  • Etv5
  • transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Cite this

The transcription factor Etv5 controls TH17 cell development and allergic airway inflammation. / Pham, Duy; Sehra, Sarita; Sun, Xin; Kaplan, Mark.

In: Journal of Allergy and Clinical Immunology, Vol. 134, No. 1, 2014.

Research output: Contribution to journalArticle

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N2 - Background The differentiation of TH17 cells, which promote pulmonary inflammation, requires the cooperation of a network of transcription factors. Objectives We sought to define the role of Etv5, an Ets-family transcription factor, in TH17 cell development and function. Methods TH17 development was examined in primary mouse T cells wherein Etv5 expression was altered by retroviral transduction, small interfering RNA targeting a specific gene, and mice with a conditional deletion of Etv5 in T cells. The direct function of Etv5 on the Il17 locus was tested with chromatin immunoprecipitation and reporter assays. The house dust mite-induced allergic inflammation model was used to test the requirement for Etv5-dependent T H17 functions in vivo. Results We identify Etv5 as a signal transducer and activator of transcription 3-induced positive regulator of T H17 development. Etv5 controls TH17 differentiation by directly promoting Il17a and Il17f expression. Etv5 recruits histone-modifying enzymes to the Il17a-Il17f locus, resulting in increased active histone marks and decreased repressive histone marks. In a model of allergic airway inflammation, mice with Etv5-deficient T cells have reduced airway inflammation and IL-17A/F production in the lung and bronchoalveolar lavage fluid compared with wild-type mice, without changes in TH2 cytokine production. Conclusions These data define signal transducer and activator of transcription 3-dependent feed-forward control of TH17 cytokine production and a novel role for Etv5 in promoting T cell-dependent airway inflammation.

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