1. Academic Validation
  2. TLRs induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface

TLRs induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface

  • Int Immunopharmacol. 2021 Nov;100:108070. doi: 10.1016/j.intimp.2021.108070.
Na Yu 1 Yiming Weng 2 Wei Liu 3 Lixia Chen 4 Furhan Iqbal 5 Zhe Yin 6 Yinyan He 7 Yanqiu Wang 8
Affiliations

Affiliations

  • 1 Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China. Electronic address: yuna117@126.com.
  • 2 Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: wym_eryida@126.com.
  • 3 Dapuqiao Community Health Service Center, Huangpu District, Shanghai, 200023, China. Electronic address: bettylliuwei@126.com.
  • 4 Department of Obstetrics & Gynecology, Songjiang maternity and child health hospital, Shanghai 201620, China.
  • 5 Institute of Pure and Applied Biology, Bahauddin Zakariya University Multan, Pakistan.
  • 6 Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: 1240805853@qq.com.
  • 7 Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Department of Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China. Electronic address: amelie0228@126.com.
  • 8 Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: wangfan2002@126.com.
Abstract

Research question: In previous studies, we demonstrated that the human decidua and decidual stromal cells express high levels of CCL2 (chemokine (C-C motif) ligand 2, also known as monocyte chemotactic protein-1) and its receptor CCR2 (Chemokine Receptor 2). DSC-derived CCL2 interacts with CCR2 on DICs, causing the production and secretion of Th2-type cytokines, which promotes a Th2 bias at the maternal-foetal interface. Many pathogens may be present in the genital tract during pregnancy, but whether they affect immune regulation, especially Th2 regulation remains unknown. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that recognise specific components of microbes and certain host molecules and play an important role in the host innate immune response. We examined TLR expression and evaluated whether TLRs could affect CCL2 secretion and subsequently induce Th1/Th2 responses.

Design: We used quantitative Real-Time PCR to measure TLR expression in the decidua and DSCs (decidual stromal cells). DSCs were cultured in the presence or absence of the TLR2 agonists PAM3CSK4, PGN-Sa, and zymosan, the TLR3 Agonist poly (I:C) and the TLR4 Agonist LPS. Then, the supernatants were assayed for CCL2 secreted by DSCs and IL-4, IFN-γ, IL-10, and TNF-α produced by DICs.

Results: Costimulation with TLR2, TLR3 and TLR4 agonists resulted in enhancing CCL2 production compared with that in the controls. Additionally, these TLR2, 3, and 4 agonists stimulated CD80/CD86 on DSCs and regulated IL-4 and IL-10 secretion on DICs. TLR2 and TLR3 agonists may promote Th1/Th2 immune bias.

Conclusions: TLRs may induce Th1/Th2 responses by affecting the secretion of CCL2 at the maternal-foetal interface.

Keywords

CCL2; Maternal-foetal interface; Th1/Th2 cytokines; Toll-like receptors.

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