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

  • Int J Biol Macromol. 2024 Sep;276(Pt 2):133994. doi: 10.1016/j.ijbiomac.2024.133994.
Li Wang  1 ,  Hui Zeng  1 ,  Hu Li  1 ,  Jingcong Dai  1 ,  Shuang You  1 ,  Huanhuan Jiang  2 ,  Quan Wei  1 ,  Zhiyong Dong  1 ,  Shuaibin Liu  1 ,  Ju Ren  1 ,  Yun Zhu  3 ,  Xia Yang  4 ,  Fan He  5 ,  Lina Hu  6
Affiliations
  • 1. Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
  • 2. Yangzhou Maternal and Child Care Service Centre, Yangzhou 225000, Jiangsu, China.
  • 3. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4. Shanxi Key Laboratory of Functional Proteins, Shanxi Jinbo Bio-Pharmaceutical Co., Ltd., Taiyuan 030032, Shanxi, China.
  • 5. The Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Joint International Research Lab for Reproduction and Development, Ministry of Education, Chongqing 400010, China; Reproduction and Stem Cell Therapy Research Center of Chongqing, Chongqing 400010, China. Electronic address: [email protected].
  • 6. The Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Joint International Research Lab for Reproduction and Development, Ministry of Education, Chongqing 400010, China; Reproduction and Stem Cell Therapy Research Center of Chongqing, Chongqing 400010, China. Electronic address: [email protected].
PMID: 39032906 DOI: 10.1016/j.ijbiomac.2024.133994
Abstract

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.

Keywords
Recombinant humanized type I collagen; Recurrent spontaneous abortion; Th17/Treg axis.
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