Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion

Autor: Xiao-Juan Wang, Wan-Li Ma, Hua Lin, Qian-Qian Xu, Zhaohui Tong, Qiong Zhou, Xiang Cheng, Huan-Zhong Shi, Xiao-Guang Jin, Xiu-Zhi Wu
Rok vydání: 2014
Předmět:
Zdroj: American Journal of Respiratory and Critical Care Medicine. 189:697-706
ISSN: 1535-4970
1073-449X
DOI: 10.1164/rccm.201310-1776oc
Popis: IFN-γ-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.To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models.The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-γ(-/-), 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.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-γ(-/-) mice, and improved survival could be seen in IFN-γ(-/-) 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-γ deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway.In mouse models of MPE, IFN-γ inhibited Th17-cell differentiation, whereas IL-17 inhibited Th1-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-γ promoted MPE formation and mouse death.
Databáze: OpenAIRE