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

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.

The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss

“…In order to confirm the robustness of the data, we compared our results with previously published data. We successfully captured all the immune cell populations consistent with previously report (36,38). We also confirmed the variations of immune cells revealed by scRNA-seq data using FACS analysis.…”

“…was diminished in proportion in RPL patients (37,38). However, the global immune variations at the maternal-fetal interface of URPL are still largely unknown.…”

Mucins produced by type II pneumocyte: culprits in SARS-CoV-2 pathogenesis

“…Thus, the activated PAMP-PRR system results in the production of IFN, which then acts on local type II pneumocytes, leading to mucus production. Indeed, we found that large amounts of IFNs are produced by AMs following SARS-CoV-2 infection 2 . Intriguingly, the virus can be amplified in AMs depending on their phenotype 2 .…”

“…Indeed, we found that large amounts of IFNs are produced by AMs following SARS-CoV-2 infection 2 . Intriguingly, the virus can be amplified in AMs depending on their phenotype 2 .…”

“…To curb infection and subsequent organic damage, a deep understanding of the pathogenetic process is highly desirable. Recently, we found that IFN-driven mucin expression in type II alveolar epithelial cells is crucial in initiating hypoxia and early lung pathology 1 , and SARS-CoV-2 is disposed of by M1 and M2 alveolar macrophages (AMs) in distinct manners 2 . In this correspondence, we propose that (1) following the invasion of the alveoli and uptake by local alveolar macrophages, SARS-CoV-2 may stimulate macrophages to produce proinflammatory cytokines, including type I interferon; (2) type I interferon acts on neighboring alveolar type II pneumocytes and activates the cytoplasmic transcription factor aryl hydrocarbon receptor (AhR); (3) subsequently, AhR is translocated to the nucleus, where it promotes the expression of mucin genes, leading to mucus production; and (4) mucus begins to accumulate in the alveoli and gradually impairs the exchange of O 2 and CO 2 , initially causing hypoxia and then dampening CO 2 exhalation, leading to a critical illness.…”