Jie Duan1, Xiao-Ping Jiang, Ming-Qing Li, Deng-Xuan Fan, Ying Wang, Da-Jin Li, Li-Ping Jin. 1. 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.
Abstract
PROBLEM: To investigate whether thymic stromal lymphopoietin (TSLP) regulates the apoptosis of decidual γδ T cells and to elucidate the mechanism. METHOD OF STUDY: 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. RESULTS: 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. CONCLUSION: 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.
PROBLEM: To investigate whether thymic stromal lymphopoietin (TSLP) regulates the apoptosis of decidual γδ T cells and to elucidate the mechanism. METHOD OF STUDY: 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. RESULTS: 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 humanTSLP. CONCLUSION: 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.