T-bet controls severity of hypersensitivity pneumonitis.
T-bet controls severity of hypersensitivity pneumonitis.
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DOI：
10.1186/1476-9255-8-15
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发表时间：
2011-06-23
期刊：
影响因子：
--
通讯作者：
Fitzpatrick EA
中科院分区：
文献类型：
--
作者：
Abdelsamed HA;Desai M;Nance SC;Fitzpatrick EA
过敏性肺炎（HP）是一种间质性肺病，在反复暴露于吸入的环境抗原后发生。该疾病的特征是肺泡炎、肉芽肿形成和在一些患者中的纤维化。IFNγ在HP中起关键作用;在没有IFNγ的情况下，不会发生肉芽肿形成。然而，最近使用HP动物模型的研究表明HP是一种Th 17疾病，这对IFNγ的作用提出了质疑。在这项研究中，我们报告说，最初IFNγ的产生是依赖于IL-18和转录因子T-bet，但随着疾病的继续，IFNγ的产生是IL-18独立的，部分依赖于T-bet。虽然IFNγ的产生是肉芽肿形成所必需的，但其作用与T-bet不同。缺乏T-bet并暴露于S.直弗吉尼亚发生更严重的疾病，其特征在于加剧的Th 17细胞应答、降低的Th 1细胞应答和肺中增加的胶原蛋白产生。T-bet介导的保护似乎不是由于保护性Th 1应答的发展;通过抑制IL-6将平衡从Th 17主导应答转移到Th 1应答也导致肺病理学。本研究的结果表明，在该模型中，Th 1和Th 17细胞都可以是致病性的，并且IFNγ和T-bet在疾病过程中发挥不同的作用。
Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFNγ plays a critical role in HP; in the absence of IFNγ granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFNγ. In this study, we report that initially IFNγ production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFNγ production is IL-18-independent and partially T-bet dependent. Although IFNγ production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFNγ and T-bet play divergent roles in the disease process.
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DOI：
10.4049/jimmunol.181.7.4733
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
通讯作者：
Zou W
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.
影响因子：
--
作者：
Chu, Cong-Qiu;Swart, David;Elkon, Keith B.
通讯作者：
Elkon, Keith B.
影响因子：
5.4
作者：
Nance, S;Cross, R;Fitzpatrick, EA
通讯作者：
Fitzpatrick, EA
影响因子：
4.4
作者：
Guo, Siqi;Cobb, Dustin;Smeltz, Ronald B.
通讯作者：
Smeltz, Ronald B.