The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

Jia Mao; Ying Feng; Xiaofeng Zhu; Fang Ma

doi:10.3390/biom13081213

The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

Biomolecules. 2023 Aug 3;13(8):1213. doi: 10.3390/biom13081213.

Authors

Jia Mao^{1

2}, Ying Feng³, Xiaofeng Zhu², Fang Ma^{1

4}

Affiliations

¹ Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
² Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, College of Life Sciences, Sichuan University, Chengdu 610064, China.
³ Department of Histology, Embryology and Neurobiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
⁴ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

Abstract

Human leukocyte antigen-G (HLA-G) is a non-classical human major histocompatibility complex (MHC-I) molecule with the membrane-bound and soluble types. HLA-G is primarily expressed by extravillous cytotrophoblast cells located at the maternal-fetal interface during pregnancy and is essential in establishing immune tolerance. This review provides a comprehensive understanding of the multiple molecular mechanisms by which HLA-G regulates the immune function of NK cells. It highlights that HLA-G binds to microRNA to suppress NK cell cytotoxicity and stimulate the secretion of growth factors to support fetal growth. The interactions between HLA-G and NK cells also activate senescence signaling, promoting spiral artery remodeling and maintaining the balance of maternal-fetal immune responses. In addition, HLA-G can inhibit the function of decidual T cells, dendritic cells, and macrophages. Overall, the interaction between trophoblast cells and immune cells mediated by HLA-G plays a crucial role in understanding immune regulation at the maternal-fetal interface and offers insights into potential treatments for pregnancy-related diseases.

Keywords: HLA-G; NK cell; immune cell; maternal-fetal immune interactions.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Arteries
Epithelial Cells*
Female
HLA-G Antigens*
Humans
Major Histocompatibility Complex
Pregnancy
Signal Transduction

Substances

HLA-G Antigens

Grants and funding

This work was funded by grants to F.M. and X.Z. from the National Key Research and Development Program of China (2018YFC1002803), to F.M. from the National Natural Science Foundation of China (31771662) and to X.Z. from the Sichuan Science and Technology Program (2021JDRC0029).