Foxp3+ T regulatory cell (Tregs) are central in the pathobiology of recurrent spontaneous abortions (RSA). Signal transducer and activator of transcription (STAT) proteins instruct Treg differentiation and polarization, but the STAT signaling architecture of Tregs in RSA and its modifications by lymphocyte immunotherapy (LIT) are yet unknown. By using single-cell phospho-specific flow cytometry we show that the STAT signaling biosignature of Tregs in women with RSA was characterized by marked downregulation of the IFNα/pSTAT1&5, IL-6/pSTAT1&3 and IL-2/pSTAT5 signaling nodes compared to age-matched fertile females. LIT partially restored all of these signaling axes in Tregs only in women who achieved pregnancy after treatment. Both the pretreatment biosignature of Tregs and its modulations by LIT were associated with therapeutic success. We conclude that STAT signaling pathways in Tregs are actively involved in the pathophysiology of RSA and may serve as a predictive tool for selecting patients who may benefit from LIT.

中文翻译：

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单细胞水平的STAT信号图揭示了FOXP3 + T调节细胞与淋巴细胞免疫治疗前后反复自然流产的关联的新见解。

Foxp3 + T调节细胞（Tregs）在复发性自然流产（RSA）的病理生物学中至关重要。信号转导和转录激活蛋白（STAT）指示Treg的分化和极化，但是RSA中Treg的STAT信号结构及其通过淋巴细胞免疫疗法（LIT）的修饰尚不清楚。通过使用单细胞磷酸化特异性流式细胞仪，我们显示，与年龄相比，患有RSA的女性中Tregs的STAT信号转导生物特征是IFNα/ pSTAT1＆5，IL-6 / pSTAT1＆3和IL-2 / pSTAT5信号转导点明显下调。匹配的可育雌性。LIT仅在治疗后怀孕的女性中部分恢复了Tregs中的所有这些信号轴。Tregs的预处理生物签名及其通过LIT的调节均与治疗成功相关。