Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin.
Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin.
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DOI：
10.4049/jimmunol.0900181
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Wynn TA
中科院分区：
文献类型：
--
作者：
Ramalingam TR;Pesce JT;Mentink-Kane MM;Madala S;Cheever AW;Comeau MR;Ziegler SF;Wynn TA
胸腺基质淋巴细胞生成素最近被确定为过敏原驱动的Th 2反应的发展的主开关。然而，胸腺基质淋巴细胞生成素（TSLP）在蠕虫诱导的Th 2反应的发展中的作用尚不清楚。在这里，使用TSLPR−/−小鼠，我们表明，虽然TSLPR信号参与了曼氏血吸虫卵诱导的CD 4 + Th 2反应的发展，但它在肺，肝和肠的Th 2依赖性病理学的发展中仅起短暂作用。在肺肉芽肿模型中进行的研究表明，虽然在经历原发性应答的TSLPR−/−小鼠中观察到IL-4/IL-13依赖性肉芽肿性炎症和组织嗜酸性粒细胞增多减少，但在继发性肉芽肿性应答期间，病变形成不受影响，即使在敲除小鼠中IL-5和IL-13适度减少。为了评估TSLPR信号传导在慢性Th 2依赖性应答发展中的重要性，TSLPR−/−小鼠也感染了S.曼氏尾蚴。在这里，在TSLPR−/−小鼠中观察到的唯一显著差异是急性感染动物的肝纤维化适度减少。纤维化的短暂减少与抗纤维化细胞因子IFN-γ的产生增加和促纤维化细胞因子IL-13的产生减少相关。尽管在慢性感染的TSLPR−/−小鼠中细胞因子反应的改变持续存在，但它未能减少肉芽肿形成或纤维化，证实TSLPR信号传导在慢性Th 2依赖性病理学的发展中发挥有限的作用。总的来说，这些研究结果表明，虽然TSLPR信号在过敏原驱动的Th 2反应中起着关键作用，但在这种慢性蠕虫感染期间，它发挥了轻微的调节活性。
Thymic stromal lymphopoietin was recently identified as a master switch for the development of allergen-driven Th2 responses. However, the role of thymic stromal lymphopoietin (TSLP) in the development of helminth-induced Th2 responses is unclear. Here, using TSLPR−/− mice, we show that while TSLPR signaling participates in the development of Schistosoma mansoni egg-induced CD4+ Th2 responses, it plays only a transient role in the development of Th2-dependent pathology in the lung, liver, and intestine. Studies conducted in a pulmonary granuloma model showed that while a reduction in IL-4/IL-13-dependent granulomatous inflammation and tissue eosinophilia was observed in TSLPR−/− mice undergoing a primary response, lesion formation was not affected during a secondary granulomatous response, even though IL-5 and IL-13 were modestly reduced in the knockout mice. To evaluate the importance of TSLPR signaling in the development of a chronic Th2-dependent response, TSLPR−/− mice were also infected with S. mansoni cercariae. Here, the only significant difference noted in TSLPR−/− mice was a modest decrease in liver fibrosis in acutely infected animals. The transient decrease in fibrosis was associated with increased production of the antifibrotic cytokine IFN-γ and decreased production of the profibrotic cytokine IL-13. Although the altered cytokine response persisted in chronically infected TSLPR−/− mice, it failed to reduce granuloma formation or fibrosis, confirming that TSLPR signaling plays a limited role in the development of chronic Th2-dependent pathology. Collectively, these findings suggest that while TSLPR signaling serves a key role in allergen-driven Th2 responses, it exerts minor regulatory activity during this chronic helminth infection.
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