Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia

Frontiers in Immunology

Immunology

Jun Yi¹  Yu Huang²  Yilin Li²  Fangyuan Luo³  Jun Yue⁴  Xinghui Liu⁵  Wenming Xu⁶  Fulin Liu⁶  Séverine Degrelle⁷  Hedia Zitouni⁸  Isabelle Hernandez⁹  Thierry Fournier⁹  Yingzhe Guo^1,10 

[1] Department of Obstetrics and Gynecology Nursing, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, China;Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, China;Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, China;Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, China;Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital of Sichuan University, Chengdu, China;Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, China;Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology, Chengdu, China;School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, China;Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital of Sichuan University, Chengdu, China;Inovarion, Paris, France;Laboratory of Human Genome and Multi-factorial Diseases, Faculty of Pharmacy of Monastir, Monastir, Tunisia;Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre & Postnatal Microbiota, Université Paris Cité, Paris, France;School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China;

关键词: preeclampsia;    placental decidua;    single-cell RNA sequencing;    immune tolerance;    maternal-fetal interface;    human leucocyte antigen;   

DOI  :  10.3389/fimmu.2023.1234577

 received in 2023-06-04, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPreeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed.MethodsSingle-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte.ResultsA total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation.ConclusionsWe revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.

【 授权许可】

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Copyright © 2023 Luo, Liu, Guo, Xu, Li, Yi, Fournier, Degrelle, Zitouni, Hernandez, Liu, Huang and Yue