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

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

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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
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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