Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma

Jung Won Park, Hyun Jung Min, Jung Ho Sohn, Joo Young Kim, Jeong Ho Hong, Kirsten S. Sigrist, Laurie H. Glimcher, Eun Sook Hwang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: A TH1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both TH1 and TH2 cytokines in TH cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce TH2 cytokines and have spontaneous airway inflammation. Objectives: We tested whether T-bet overexpression could protect against the development or progression of asthma. Methods: We generated a T cell-specific and inducible line of T-bet-transgenic mice on a T-bet-deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)-induced asthma model. Results: Induction of T-bet in a T cell-specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and TH2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as TH2 cytokine production. Conclusions: Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma.

Original languageEnglish
Pages (from-to)479-485.e6
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number2
DOIs
Publication statusPublished - 2009 Feb

Keywords

  • OVA
  • T cell
  • T-bet
  • airway hyperresponsiveness
  • asthma
  • transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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