Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Yangzhou Maternal and Child Care Service Centre, Yangzhou 225000, Jiangsu, China.
Int J Biol Macromol. 2024 Sep;276(Pt 2):133994. doi: 10.1016/j.ijbiomac.2024.133994. Epub 2024 Jul 18.
Disruption of the extracellular matrix and dysregulation of the balance between Th17 and regulatory T cells are recognized as risk factors for recurrent spontaneous abortion (RSA). However, the interaction between matrix components and the Th17/Treg axis remains poorly elucidated. The result of this study revealed that the absence of type I collagen in the decidua is linked to Th17/Treg imbalance in RSA. Furthermore, we discovered that biomaterial recombinant humanized type I collagen (rhCOLI) promoted T cell differentiation into Tregs by inhibition the Notch1/Hes1 signaling pathway and enhanced the immunosuppressive function of Tregs, as indicated by increased secretion level of IL-10 and TGF-β. Importantly, this study is the first to demonstrate that rhCOLI can modulate the Th17/Treg imbalance, reduce embryo resorption rates, reshape the immune microenvironment at the maternal-fetal interface, and improve fertility in an RSA mouse model. Collectively, these findings suggest that type I collagen deficiency may contribute to, rather than result from, RSA, and propose a potential intervention for RSA using rhCOLI.
细胞外基质的破坏和 Th17 与调节性 T 细胞之间平衡的失调被认为是复发性自然流产（RSA）的危险因素。然而，基质成分与 Th17/Treg 轴之间的相互作用仍未得到充分阐明。本研究结果表明，蜕膜中 I 型胶原的缺失与 RSA 中的 Th17/Treg 失衡有关。此外，我们发现生物材料重组人源化 I 型胶原（rhCOLI）通过抑制 Notch1/Hes1 信号通路促进 T 细胞向 Treg 分化，并增强 Treg 的免疫抑制功能，表现为 IL-10 和 TGF-β分泌水平增加。重要的是，这项研究首次表明 rhCOLI 可以调节 Th17/Treg 失衡，降低胚胎吸收率，重塑母体-胎儿界面的免疫微环境，提高 RSA 小鼠模型的生育能力。综上所述，这些发现表明 I 型胶原缺乏可能导致 RSA，而不是 RSA 的结果，并提出了使用 rhCOLI 治疗 RSA 的潜在干预措施。
