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Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface

  • Jin Soo Joo (Department of Systems Biology, Yonsei University) ;
  • Dongeun Lee (Department of Systems Biology, Yonsei University) ;
  • Jun Young Hong (Department of Systems Biology, Yonsei University)
  • Received : 2024.04.12
  • Accepted : 2024.07.08
  • Published : 2024.08.31
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Abstract

Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.

Keywords

Acknowledgement

We apologize that we cannot cite all the seminal papers on this subject. This work was supported by the Yonsei Research Fund (2023-22-0102), Young Medical Scientist Research Grant through the Daewoong Foundation (DFY2301P), and the National Research Foundation of Korea, Ministry of Science, Information and Communication Technology (ICT) and Future Planning NRF-2022R1C1C1007283.

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