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

J Allergy Clin Immunol. 2014 Jul;134(1):204-14. doi: 10.1016/j.jaci.2013.12.021. Epub 2014 Jan 31.


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 TH17 functions in vivo.

Results: We identify Etv5 as a signal transducer and activator of transcription 3-induced positive regulator of TH17 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.

Keywords: Etv5; T(H)17 cells; allergic inflammation; epigenetic modifications; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / chemistry
  • Allergens / immunology
  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Gene Expression Regulation
  • Genetic Loci
  • Genetic Vectors
  • Histones / genetics
  • Histones / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Pneumonia / genetics*
  • Pneumonia / immunology
  • Pneumonia / pathology
  • Primary Cell Culture
  • Pyroglyphidae / chemistry
  • Pyroglyphidae / immunology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / immunology
  • Respiratory Hypersensitivity / genetics*
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / pathology
  • Retroviridae / genetics
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology*
  • Signal Transduction
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / immunology*


  • Allergens
  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Histones
  • Il17a protein, mouse
  • Il17f protein, mouse
  • Interleukin-17
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Transcription Factors