T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways.
BACKGROUND
Previous studies have shown that mice lacking T-bet, a critical transcription factor for T(H)1 cell differentiation, spontaneously develop airway inflammation with intense eosinophil infiltrates. However, the mechanism underlying T-bet-mediated inhibition of allergic airway inflammation is still unknown.


OBJECTIVE
To determine the regulatory role of T-bet in antigen-induced allergic airway inflammation.


METHODS
We examined the role of T-bet in antigen-induced allergic airway inflammation using T-bet(-/-) mice on a BALB/c background that did not develop spontaneous airway inflammation. We also examined the role of T-bet expression of CD4(+) T cells in airway inflammation by adoptive transfer experiments.


RESULTS
We found that antigen-induced eosinophil recruitment, goblet cell hyperplasia, and T(H)2 cytokine production in the airways were enhanced in T-bet(-/-) mice. However, in the absence of signal transducer and activator of transcription 6 (STAT6), T-bet deficiency could not induce the antigen-induced eosinophilic airway inflammation. Adoptive transfer of T-bet(-/-) or T-bet(+/+) CD4(+) T cells to T-bet(-/-)Rag-2(-/-) mice revealed that the expression of T-bet in CD4(+) T cells was vital for the inhibition of antigen-induced eosinophilic airway inflammation. Interestingly, antigen-induced neutrophil recruitment in the airways was also enhanced in T-bet(-/-) mice. Moreover, T-bet(-/-) CD4(+) T cells preferentially differentiated into IL-17-producing cells that mediated neutrophilic airway inflammation.


CONCLUSIONS
T-bet inhibits both T(H)2 cell-mediated eosinophilic inflammation and T(H)17 cell-mediated neutrophilic inflammation in the airways.


CONCLUSIONS
The dysfunction of T-bet may be involved in the pathogenesis of severe asthma, in which accumulation of neutrophils as well as eosinophils in the airways is a hallmark of disease.
Fujiwara
Michio
M
Department of Allergy and Clinical Immunology, Clinical Cell Biology, Chiba University, Chiba, Japan.
Hirose
Koichi
K
Kagami
Shin-ichiro
S
Takatori
Hiroaki
H
Wakashin
Hidefumi
H
Tamachi
Tomohiro
T
Watanabe
Norihiko
N
Saito
Yasushi
Y
Iwamoto
Itsuo
I
Nakajima
Hiroshi
H
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics; D004804:Eosinophils / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D014132:Trachea / Q000276:immunology; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; D018793:Interleukin-13; D020381:Interleukin-17; C499308:Rag2 protein, mouse; D050800:STAT6 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor