Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, PR China.
Am J Respir Crit Care Med. 2012 Dec 1;186(11):1168-79. doi: 10.1164/rccm.201207-1307OC. Epub 2012 Oct 11.
IL-9-producing CD4(+) T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated.
To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells.
Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated.
The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers.
Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.
已报道产生白细胞介素-9（IL-9）的 CD4(+)T 细胞（Th9 细胞）参与炎症和自身免疫性疾病。然而，Th9 细胞在恶性肿瘤中的作用尚未得到研究。
阐明 Th9 细胞在恶性胸腔积液（MPE）中分化的机制，并探讨 Th9 细胞对肺癌细胞的免疫调节作用。
确定 Th9 细胞在 MPE 和血液中的 Th17 和 Th1 细胞中的分布。体外研究促炎细胞因子和调节性 T 细胞对 Th9 细胞分化的影响和机制。还研究了 IL-9、IL-17 和 IFN-γ 对肺癌细胞系的影响和信号转导。
与血液相比，MPE 中 Th9、Th17 和 Th1 细胞的数量均增加。MPE 中 Th9 细胞的增加是由于细胞因子和调节性 T 细胞的促进作用。通过激活 STAT3 信号，IL-9 和 IL-17 均可显著促进肺癌细胞的增殖和迁移活性，而激活 STAT1 信号的 IFN-γ 则可抑制肺癌细胞的增殖和迁移。IFN-γ 可诱导肺癌细胞凋亡。此外，IL-9 和 IFN-γ（而非 IL-17）可强烈促进肺癌细胞与胸膜间皮细胞单层的细胞间黏附。
我们的数据表明 Th9 细胞在 MPE 中增加，并且 Th9 细胞在人类肿瘤环境中对肺癌细胞发挥重要的免疫调节作用。
