American journal of reproductive immunology (New York, N.Y. : 1989) · 2013
Thymic stromal lymphopoietin suppresses the apoptosis of decidual gamma-delta T cells via regulation of the signal transduction and activation of transcription 3/caspase-3 signaling pathway.
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Duan Jie, Jiang Xiao-Ping, Li Ming-Qing, Fan Deng-Xuan, Wang Ying, Li Da-Jin, Jin Li-Ping
Аннотация
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.
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.