Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

Chuang Guo,Jun Lin,Xianhong Tong,Chen Jiang,Qiaoni Yu,Haiming Wei,Zhutian Zeng,Kun Li,Qing Sha,Fangting Lu,Pengfei Cai,Qian Liu,Dandan Zong,Yanshi Wang,Jingwen Fang,Daojing Li,Wen Zhang,Lü Li ,Lina Jin ,Kun Qu

doi:10.1038/s41421-020-00236-z

Abstract

Maintaining homeostasis of the decidual immune microenvironment at the maternal–fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.

Highlights

Recurrent pregnancy loss (RPL), defined as loss of two or more consecutive pregnancies, affects up to 5% of women trying to conceive[1,2]
Low-quality cells were filtered after rigorous quality control (QC) definition (Supplementary Fig. S1a–d), and we retained a total of 18,646 high-quality CD45+ single transcriptomes
Similar to recently reported findings, we found that dNK cells25: CD39+ CD18− CD103− (dNK1) cells expressed high levels of KIR gene family members, suggesting that dNK1 cells are likely recognized by extravillous trophoblasts (EVTs) (Supplementary Fig. S4c, d). dNK1 cells expressed LILRB1 (Supplementary Fig. S4e, f), which binds to HLAG proteins expressed on trophoblast cells to increase the secretion of growth-supporting factors[31]

Summary

Introduction

Recurrent pregnancy loss (RPL), defined as loss of two or more consecutive pregnancies, affects up to 5% of women trying to conceive[1,2]. Decidual macrophages comprise approximately 10–20% of decidual leukocytes during the first trimester of pregnancy and have been reported to function as antiinflammatory cells with M2-like phenotypes[12,13,14]. Decidual macrophages are known to have many functions similar to those of dNK cells, including remodeling of spiral arteries, trophoblast invasion, promotion of angiogenesis, hindering T cell activation, and mediating canonical responses to antimicrobial infections[16,17,18]. Decidual T cells have functional roles in both normal and pathological pregnancies[19]. These maternal leukocytes, together with decidual stromal cells and extravillous trophoblasts (EVTs), interact with each other to form a highly complex immune microenvironment[5,20]

Methods

Results

Conclusion