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

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

Author information

1
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind.
2
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
3
Laboratory of Genetics, University of Wisconsin-Madison, Wis.
4
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Ind. Electronic address: mkaplan2@iupui.edu.

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 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

PMID:
24486067
PMCID:
PMC4209254
DOI:
10.1016/j.jaci.2013.12.021
[Indexed for MEDLINE]
Free PMC Article

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