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MregDCs induce abnormal T cell functions in endometriosis

ABSTRACT: Endometriosis has a metastatic implantation biology as malignant tumors and an immunological environment as immune escape. However, the role of dendritic cells (DCs) in endometriosis is still unknown. We applied single-cell RNA sequencing (scRNA-seq) on eutopic endometrium and ectopic lesions to dissect heterogeneity within DCs subsets. ScRNA-seq data in public database was also included in the analysis. Flow cytometry was used to identify the presence of ‘mature DCs enriched in immunoregulatory molecules’ (mregDCs) in patient tissues. Multiplex immunofluorescence tissue staining was adopted to show the presence of mregDCs. To further explore the function of mregDCs in endometriosis, mregDCs and naïve CD4+ T cells were sorted by fluorescence activated cell sorting (FACS) and co-cultured. carboxyfluorescein succinimidyl ester (CFSE) assays and intracellular cytokine staining assays were employed to detect proliferation and differentiation ability of naïve CD4+ T cells in vitro. The proportions of T cell subsets in the ectopic lesions of mice following peritoneal transfusion of mregDCs were measured in vivo in a mouse model for endometriosis. ScRNA-seq data analysis displayed the substantial alterations and heterogeneity of DCs subsets in endometriosis. The proportion of mregDCs were up-regulated in the endometriosis scRNA-seq data. Flow cytometry and immunofluorescence staining confirmed the presence and upregulation of the mregDCs in ectopic lesions. The co-cultured experiment showed that endometriosis-associated mregDCs have the ability to induce naïve CD4+ T cells proliferation and differentiating as Th2 and iTregs. After peritoneal transfusion of mregDCs into endometriosis mouse model, the number of Th2 in ectopic lesion increased significantly. Our research revealed the heterogeneity of DCs landscape in endometriosis in single cell level. We found the specific mregDC celltype may participate in the abnormal inflammation environment in endometriosis and exert profound immunostimulatory and regulatory changes in T cells function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262645 | GEO | 2026/07/26

REPOSITORIES: GEO

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Project description:Endometriosis is a debilitating gynecological disorder affecting approximately 10% of the female population. Despite its prevalence, robust methods to classify and treat endometriosis remain elusive. Changes throughout the menstrual cycle in tissue size, architecture, cellular composition, and individual cell phenotypes make it extraordinarily challenging to identify markers or cell types associated with uterine pathologies since disease-state alterations in gene and protein expression are convoluted with cycle phase variations. Here, we developed an integrated workflow to generate both proteomic and single-cell RNA-sequencing (scRNA-seq) data sets using tissues and cells isolated from the uteri of control and endometriotic donors. Using a linear mixed effect model (LMM), we identified proteins associated with cycle stage and disease, revealing a set of genes that drive separation across these two biological variables. Further, we analyzed our scRNA-seq data to identify cell types expressing cycle and disease- associated genes identified in our proteomic data. A module scoring approach was used to identify cell types driving the enrichment of certain biological pathways, revealing several pathways of interest across different cell subpopulations. Finally, we identified ligand-receptor pairs including Axl/Tyro3 – Gas6, that may modulate interactions between endometrial macrophages and/or endometrial stromal/epithelial cells. Analysis of these signaling pathways in an independent cohort of endometrial biopsies revealed a significant decrease in Tyro3 expression in patients with endometriosis compared to controls, both transcriptionally and through histological staining. This measured decrease in Tryo3 in patients with disease could serve as a novel diagnostic biomarker or treatment avenue for patients with endometriosis. Taken together, this integrated approach provides a framework for integrating LMMs, proteomic and RNA-seq data to deconvolve the complexities of complex uterine diseases and identify novel genes and pathways underlying endometriosis.

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MregDCs induce abnormal T cell functions in endometriosis

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