Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion
Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion
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恶性胸腔积液小鼠模型中 Th1 和 Th17 细胞的相互作用
DOI：
10.1164/rccm.201310-1776oc
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发表时间：
2014-03-15
影响因子：
24.7
通讯作者：
Shi, Huan-Zhong
中科院分区：
文献类型：
--
作者：
Lin, Hua;Tong, Zhao-Hui;Shi, Huan-Zhong
理由：产生IFN-γ的CD 4（+）T（Th 1）细胞和产生IL-17的CD 4（+）T（Th 17）细胞与多种恶性肿瘤有关，但恶性胸腔积液（MPE）中Th 1和Th 17细胞之间的相互关系尚待阐明。目的：探讨Th 1和Th 17细胞在小鼠MPE发病过程中的分化和免疫调节作用。在IFN-γ（-/-）、IL-17（-/-）和野生型小鼠中研究MPE中Th 1和Th 17细胞的分布和分化。Th 1和Th 17细胞对MPE的发展和MPE荷瘤小鼠的生存的影响也被lowed. Measures和主要结果：我们已经证明，增加Th 1和Th 17细胞可以被发现在MPE相比，血液和脾脏。与野生型小鼠相比，IFN-γ（-/-）小鼠MPE中Th 17细胞显著增加，IFN-γ（-/-）小鼠存活率提高。IL-17（-/-）小鼠MPE中Th 1细胞数量增加，IL-17（-/-）小鼠存活率降低。体外实验表明，IFN-γ缺乏通过抑制STAT 3通路促进Th 17细胞分化，IL-17缺乏通过抑制STAT 1通路促进Th 1细胞分化。结论：在MPE小鼠模型中，IFN-γ抑制Th 17细胞分化，而IL-17抑制Th 1细胞分化。IL-17可抑制MPE的形成并提高MPE小鼠的存活率;相反，IFN-γ可促进MPE的形成和小鼠死亡。
Rationale: IFN-gamma-producing CD4(+) T (Th1) cells and IL-17-producing CD4(+) T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Th1 and Th17 cells in malignant pleural effusion (MPE) remains to be elucidated.Objectives: To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models.Methods: The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-gamma(-/-), IL-17(-/-) and wild-type mice. The effects of Th1 and Th17 cells on the development of MPE and the survival of mice bearing MPE were also investigated.Measurements and Main Results: We have demonstrated that increased Th1 and Th17 cells could be found in MPE as compared with blood and spleen. Compared with wild-type mice, Th17 cells were markedly augmented in MPE from IFN-gamma(-/-)mice, and improved survival could be seen in IFN-gamma(-/-) mice. Th1 cell numbers were elevated in MPE from IL-17(-/-) mice, and decreased survival could be seen in IL-17(-/-) mice. The in vitro experiments showed that IFN-gamma deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway.Conclusions: In mouse models of MPE, IFN-gamma inhibited Th17-cell differentiation, whereas IL-17 inhibited Thl-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-gamma promoted MPE formation and mouse death..