信号转导和转录激活因子4与原因不明复发性流产

Signal Transducer and Activator of Transcription 4 and Unexplained Recurrent Spontaneous Abortion

信号转导和转录激活因子4(STAT4)信号转导途径是人体生理与病理反应的共同通路之一,与细胞生长、增殖、分化密切相关。复发性自然流产(RSA)的病因复杂,但近50%RSA原因不明。辅助性T细胞1型(Th1)和Th2失衡是RSA的重要特征,近年通过对小鼠研究发现,STAT4缺陷小鼠表现Th2免疫应答优势,STAT6缺陷小鼠表现Th1免疫优势,认为STAT4途径是细胞因子调节免疫细胞向Th1分化的最主要的信号转导通路。白细胞介素12(IL-12)是维持Th1/Th2平衡的中心环节,与RSA密切相关。研究发现,STAT4是IL-12调节的关键媒介,其介导的IL-12信号通路可能是RSA的发病机制之一。

The signal transducer and activator of transcription 4（STAT4） signal transduction pathway regulates cell growth, proliferation and differentiation. The causes of recurrent spontaneous abortion （RSA） are complicated, with almost 50% of RSA remaining unexplained. However, it is known that there is a significant imbalance between type 1 helper T cell （Thl） and type 2 helper T cell （Th2） differentiation associated with RSA. Recent studies in STAT4-deficient mice demonstrated that there is an enhan.ced Th2 immune response, while STAT6-deficient mice demonstrated an enhanced Thl response. The STAT4 pathway is one of the major pathways by which cytokines regulate the differentiation of immune cells. For example, interleukin-12 （IL-12） maintains the balance between Th1/ Th2, and STAT4 the central link to the cytokine＇s signaling. Moreover, alterations in both IL-12 and STAT4 are commonly observed in RSA. In fact, the regulation of IL-12 by STAT4 may underlie the pathogenesis of RSA.