Recombinant humanized type I collagen remodels decidual immune microenvironment at maternal-fetal interface by modulating Th17/Treg imbalance

• Published in: International journal of biological macromolecules 2024-09, Vol.276 (Pt 2), p.133994, Article 133994
• Main Authors: Wang, Li, Zeng, Hui, Li, Hu, Dai, Jingcong, You, Shuang, Jiang, Huanhuan, Wei, Quan, Dong, Zhiyong, Liu, Shuaibin, Ren, Ju, Zhu, Yun, Yang, Xia, He, Fan, Hu, Lina
• Format: Article
• Language: English
• Subjects: Recombinant humanized type I collagen; Recurrent spontaneous abortion; Th17/Treg axis
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133994

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.