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

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Allergens
Asthma
T-Lymphocytes
Proteins
Ovalbumin
Cytokines
Inflammation
Goblet Cells
Interleukin-13
Interleukin-5
Bronchoalveolar Lavage Fluid
Immunoglobulin E
Transgenic Mice
Hyperplasia
Cell Differentiation
Transcription Factors

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma. / Park, Jung Won; Min, Hyun Jung; Sohn, Jung Ho; Kim, Joo Young; Hong, Jeong-Ho; Sigrist, Kirsten S.; Glimcher, Laurie H.; Hwang, Eun Sook.

In: Journal of Allergy and Clinical Immunology, Vol. 123, No. 2, 01.02.2009.

Research output: Contribution to journalArticle

Park, Jung Won ; Min, Hyun Jung ; Sohn, Jung Ho ; Kim, Joo Young ; Hong, Jeong-Ho ; Sigrist, Kirsten S. ; Glimcher, Laurie H. ; Hwang, Eun Sook. / Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 123, No. 2.
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