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

doi:10.1016/j.jaci.2008.10.035

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 journal › Article › peer-review

19 Citations (Scopus)

Abstract

Background: A T_H1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both T_H1 and T_H2 cytokines in T_H cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce T_H2 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_H2 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_H2 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 language	English
Pages (from-to)	479-485.e6
Journal	Journal of Allergy and Clinical Immunology
Volume	123
Issue number	2
DOIs	https://doi.org/10.1016/j.jaci.2008.10.035
Publication status	Published - 2009 Feb

Bibliographical note

Funding 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.).

Keywords

OVA
T cell
T-bet
airway hyperresponsiveness
asthma
transgenic mice

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.jaci.2008.10.035

Cite this

@article{86b785d4dea24a7cbcf9f27da74e125c,

title = "Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma",

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.",

keywords = "OVA, T cell, T-bet, airway hyperresponsiveness, asthma, transgenic mice",

author = "Park, {Jung Won} and Min, {Hyun Jung} and Sohn, {Jung Ho} and Kim, {Joo Young} and Hong, {Jeong Ho} and Sigrist, {Kirsten S.} and Glimcher, {Laurie H.} and Hwang, {Eun Sook}",

note = "Funding 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.). ",

year = "2009",

month = feb,

doi = "10.1016/j.jaci.2008.10.035",

language = "English",

volume = "123",

pages = "479--485.e6",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma

AU - Park, Jung Won

AU - Min, Hyun Jung

AU - Sohn, Jung Ho

AU - Kim, Joo Young

AU - Hong, Jeong Ho

AU - Sigrist, Kirsten S.

AU - Glimcher, Laurie H.

AU - Hwang, Eun Sook

N1 - Funding 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.).

PY - 2009/2

Y1 - 2009/2

N2 - 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.

AB - 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.

KW - OVA

KW - T cell

KW - T-bet

KW - airway hyperresponsiveness

KW - asthma

KW - transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=59449090710&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2008.10.035

DO - 10.1016/j.jaci.2008.10.035

M3 - Article

C2 - 19081613

AN - SCOPUS:59449090710

SN - 0091-6749

VL - 123

SP - 479-485.e6

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this