Duan Jie, Jiang Xiao-Ping, Li Ming-Qing, Fan Deng-Xuan, Wang Ying, Li Da-Jin, Jin Li-Ping
Laboratory for Reproductive Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Am J Reprod Immunol. 2013 Dec;70(6):464-71. doi: 10.1111/aji.12158. Epub 2013 Sep 13.
To investigate whether thymic stromal lymphopoietin (TSLP) regulates the apoptosis of decidual γδ T cells and to elucidate the mechanism.
Primary human decidual γδ T cells were treated with TSLP only or TSLP combined with different signaling inhibitors (STAT3, STAT5, AKT, and ERK). The levels of signal transduction and activation of transcription 3 (STAT3) tyrosine phosphorylation and caspase3 expression were determined using Western blot analysis, and the apoptosis of decidual γδ T cells was analyzed by flow cytometry.
The proportions of γδ T cells in the peripheral circulation and in decidual CD3(+) cell population in women with normal pregnancy were higher than the proportions of γδ T cells in either non-pregnant control or miscarriage. Decidual γδ T cells co-expressed the TSLP receptors (TSLPR) and IL-7Rα, and the expression of TSLPR in decidual γδ T cells was higher than that in decidual CD8(+) and CD4(+) T cells. Treatment with TSLP significantly suppressed the apoptosis of decidual γδ T cells and enhanced STAT3 phosphorylation. Moreover, STAT3, and not other inhibitors, completely abrogated the anti-apoptotic effect and expression of caspase3 in decidual γδ T cells induced by recombinant human TSLP.
These results suggest that TSLP may down-regulate caspase3 expression through activation of the STAT3 pathway, thereby suppressing the apoptosis of decidual γδ T cells.
研究胸腺基质淋巴细胞生成素（TSLP）是否调节蜕膜γδ T细胞的凋亡并阐明其机制。
将原代人蜕膜γδ T细胞单独用TSLP处理或与不同的信号抑制剂（STAT3、STAT5、AKT和ERK）联合处理。使用蛋白质免疫印迹分析测定信号转导和转录激活因子3（STAT3）酪氨酸磷酸化水平以及半胱天冬酶3（caspase3）的表达，并通过流式细胞术分析蜕膜γδ T细胞的凋亡情况。
正常妊娠女性外周循环和蜕膜CD3(+)细胞群中γδ T细胞的比例高于非妊娠对照组或流产组中的γδ T细胞比例。蜕膜γδ T细胞共表达TSLP受体（TSLPR）和IL-7Rα，且蜕膜γδ T细胞中TSLPR的表达高于蜕膜CD8(+)和CD4(+) T细胞中的表达。用TSLP处理可显著抑制蜕膜γδ T细胞的凋亡并增强STAT3磷酸化。此外，STAT3而非其他抑制剂完全消除了重组人TSLP诱导的蜕膜γδ T细胞中的抗凋亡作用和caspase3的表达。
这些结果表明，TSLP可能通过激活STAT3途径下调caspase3表达，从而抑制蜕膜γδ T细胞的凋亡。
