| First Author | Pham D | Year | 2014 |
| Journal | J Allergy Clin Immunol | Volume | 134 |
| Issue | 1 | Pages | 204-14 |
| PubMed ID | 24486067 | Mgi Jnum | J:275369 |
| Mgi Id | MGI:6304355 | Doi | 10.1016/j.jaci.2013.12.021 |
| Citation | Pham D, et al. (2014) The transcription factor Etv5 controls TH17 cell development and allergic airway inflammation. J Allergy Clin Immunol 134(1):204-14 |
| abstractText | 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. |
