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

Authors
 Jung Won Park  ;  Hyun Jung Min  ;  Jung Ho Sohn  ;  Joo Young Kim  ;  Jeong Ho Hong  ;  Kirsten S. Sigrist  ;  Laurie H. Glimcher  ;  Eun Sook Hwang 
Citation
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.123(2) : 479-485, 2009 
Journal Title
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
ISSN
 0091-6749 
Issue Date
2009
MeSH
Allergens/immunology ; Animals ; Asthma/immunology* ; Asthma/metabolism ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/immunology ; Cytokines/drug effects ; Cytokines/immunology* ; Cytokines/metabolism ; Disease Models, Animal ; Doxycycline/pharmacology ; Eosinophilia/immunology ; Eosinophilia/metabolism ; Goblet Cells/immunology ; Goblet Cells/pathology ; Immunoglobulin E/blood ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Ovalbumin/immunology ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism* ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology* ; T-Lymphocytes/metabolism ; Th2 Cells/drug effects ; Th2 Cells/immunology* ; Th2 Cells/metabolism
Keywords
T-bet ; T cell ; transgenic mice ; OVA ; asthma ; airway hyperresponsiveness
Abstract
BACKGROUND: A T(H)1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both T(H)1 and T(H)2 cytokines in T(H) cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce T(H)2 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 T(H)2 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 T(H)2 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0091674908018897
DOI
10.1016/j.jaci.2008.10.035
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영)
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Sohn, Jung Ho(손정호)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104920
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