The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) is a common fertility problem that affects 1%-2% of couples all over the world. Despite exciting discoveries regarding the important roles of the decidual natural killer cell (dNK) and regulatory T cell in pregnancy, the immune heterogeneity in patients with unexplained recurrent pregnancy loss (URPL) remains elusive. Here, we profiled the transcriptomes of 13,953 CD45+ cells from three normal and three URPL deciduas. Based on our data, the cellular composition revealed three major populations of immune cells including dNK cell, T cell, and macrophage, and four minor populations including monocytes, dendritic cell (DC), mast cell, and B cell. Especially, we identified a subpopulation of CSF1+ CD59+ KIRs-expressing dNK cells in normal deciduas, while the proportion of this subpopulation was decreased in URPL deciduas. We also identified a small subpopulation of activated dDCs that were accumulated mainly in URPL deciduas. Furthermore, our data revealed that in decidua at early pregnancy, CD8+ T cells exhibited cytotoxic properties. The decidual macrophages expressed high levels of both M1 and M2 feature genes, which made them unique to the conventional M1/M2 classification. Our single-cell data revealed the immune heterogeneity in decidua and the potentially pathogenic immune variations in URPL.

The New Old CD8+ T Cells in the Immune Paradox of Pregnancy

“… Single-cell transcriptomic analysis of decidual CD8+ T cells from publicly available database. (A) UMAP visualization of ∼735 live MS4A7- CD3E+ CD8A+ single cell transcriptomes obtained from the decidua of three healthy first trimester pregnancy samples ( 15 ). Each symbol (circle) represents a cell, and the colors indicate the eight clusters identified by Seurat.…”

“…This diversification is likely due to the small number of markers that can be simultaneously detected in different biological settings, such as different stages of pregnancy and pathologies, resulting in arbitrary new findings or markers and cytokines, not completely grasping the whole picture. The publicly available single cell RNA sequencing datasets on decidual immune cells include insufficient CD8+ T cells for an in-depth analysis ( 15 ). Therefore, single cell RNA sequencing tailored to CD8+ T cells, e.g.…”

“…In general, investigations of the decidual CD8+ T cell compartment have largely complied with a selection of methods and markers (Supplementary Table 1, Supplementary Figure 1) that allows for a relatively unifying interpretation of their differentiation profile. In order to compare this information about decidual CD8+ T cell subsets, we re-analysed data on first trimester CD8+ T cell single cell transcriptome, published by Chen et al (15) and report the findings about equivalent populations that are described in the literature.…”

“…In order to compare this information about decidual CD8+ T cell subsets, we re-analysed data on first trimester CD8+ T cell single cell transcriptome, published by Chen et al. ( 15 ) and report the findings about equivalent populations that are described in the literature.…”

Deciphering the Intercellular Communication Network of Peripartum Decidua that Orchestrates Delivery

“…The decidua mediates communication between two semiallogenic individuals, the mother and the fetus, which is the epitome of intercellular communication (Iliodromiti et al, 2012;Pavličev et al, 2017). Therefore, the further elucidation of the intercellular communication in the decidua could facilitate our understanding of the fundamental basis of pregnancy and help to reveal pathogenic mechanisms of pregnancy-related disorders (Zhang et al, 2021b;Chen et al, 2021). Intercellular communication network analysis using scRNA-seq of human term placenta has found that the decidua is the center of intercellular signal transduction and has indicated the dominant role of growth factors and immune signals in the intercellular crosstalk (Tsang et al, 2017).…”