Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Cell Immunol. 2013 Feb;281(2):101-10. doi: 10.1016/j.cellimm.2013.03.002. Epub 2013 Mar 28.
T helper 17 (Th17) cells, which produce interleukin 17 (IL-17), are involved in the pathogenesis of autoimmune diseases and inflammatory conditions. Th17 cells have been detected in many Fas ligand-positive tumors. This study investigates the expression of Th17-related genes in PHA/IL-2-activated human T cells upon Fas ligation. Activated T cells transiently express RORγt, IL-17A, and IL-17F. A subsequent Fas receptor stimulation or contact with FasL-expressing glioma cells significantly prolongs the induction of RORγt and Th17-related cytokines. Treatments with inhibitors of caspase-1 and Stat3 reduce the Fas-signal-associated induction of RORγt, IL-17A, and IL-17F, as well as the phosphorylation of Stat3. Although the ligation of Fas results in caspase-8 cleavage and ERK1/2 phosphorylation, inhibitors for caspase-8 and MEK have no effect on the expressions of RORγt, IL-17A, and IL-17F. The results suggest that the Fas signal favors the Th17-phenotypic features of human T cells through the caspase-1/Stat3 signaling pathway.
辅助性 T 细胞 17（Th17）细胞产生白细胞介素 17（IL-17），参与自身免疫性疾病和炎症性疾病的发病机制。许多 Fas 配体阳性肿瘤中都检测到了 Th17 细胞。本研究探讨了 Fas 配体结合后 PHA/IL-2 激活的人 T 细胞中 Th17 相关基因的表达。活化的 T 细胞短暂表达 RORγt、IL-17A 和 IL-17F。随后 Fas 受体刺激或与 FasL 表达的神经胶质瘤细胞接触，显著延长了 RORγt 和 Th17 相关细胞因子的诱导。用 caspase-1 和 Stat3 的抑制剂处理可降低 Fas 信号相关的 RORγt、IL-17A 和 IL-17F 的诱导，以及 Stat3 的磷酸化。虽然 Fas 的结合导致 caspase-8 的切割和 ERK1/2 的磷酸化，但 caspase-8 和 MEK 的抑制剂对 RORγt、IL-17A 和 IL-17F 的表达没有影响。结果表明，Fas 信号通过 caspase-1/Stat3 信号通路有利于人 T 细胞的 Th17 表型特征。
