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J Allergy Clin Immunol. 2007 Mar;119(3):662-70.

T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways.

Author information

1
Department of Allergy and Clinical Immunology, Clinical Cell Biology, Chiba University, Chiba, Japan.

Abstract

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.

CONCLUSION:

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

CLINICAL IMPLICATIONS:

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.

PMID:
17336616
DOI:
10.1016/j.jaci.2006.12.643
[Indexed for MEDLINE]

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