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  • Title: T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways.
    Author: Fujiwara M, Hirose K, Kagami S, Takatori H, Wakashin H, Tamachi T, Watanabe N, Saito Y, Iwamoto I, Nakajima H.
    Journal: J Allergy Clin Immunol; 2007 Mar; 119(3):662-70. PubMed ID: 17336616.
    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.
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