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


OBJECTIVE
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.
Park
Jung Won
JW
Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
Min
Hyun Jung
HJ
Sohn
Jung Ho
JH
Kim
Joo Young
JY
Hong
Jeong Ho
JH
Sigrist
Kirsten S
KS
Glimcher
Laurie H
LH
Hwang
Eun Sook
ES
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000485:Allergens; D016207:Cytokines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007073:Immunoglobulin E; D010047:Ovalbumin; D004318:Doxycycline