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.
Bibliographical noteFunding Information:
Supported by the Korea Research Foundation (2006-E00100); the National Research & Development Program for Cancer Control, Ministry for Health, Welfare, and Family Affairs (0620380); the National Core Research Center program of the Ministry of Education, Science & Technology and the Korean Science and Engineering Foundation (R15-2006-020 to E.S.H.); and National Institutes of Health grant U19 AI031541 (to L.H.G.). This work was also supported by a grant from Yonsei University College of Medicine (to J.W.P.).
- T cell
- airway hyperresponsiveness
- transgenic mice
ASJC Scopus subject areas
- Immunology and Allergy