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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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
State	Published - Feb 2009

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

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10.1016/j.jaci.2008.10.035

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@article{a91a03418ff04d8bbc677bbaf154389d,

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",

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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

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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

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