Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women With Endometriosis

Abstract

Endometriosis is an oestrogen-dependent chronic inflammatory process with primary symptoms including dysmenorrhea, chronic pelvic pain, and infertility. The immune environment of the endometrium is essential for successful embryo implantation and ongoing pregnancy. In this study, we assessed the composition, density, and distribution of infiltrating immune cells in the endometria of women with endometriosis. Gene expression profiles of endometrial samples were downloaded from the Gene Expression Omnibus (GEO) database. We found that the TNF signalling pathway, the IL-17 signalling pathway, and the MAPK signalling pathway were significantly enriched in the eutopic endometria of women with endometriosis. The fractions and proportion of infiltrating immune cells were estimated by the CIBERSORT, MCP-counter, and ImmuCellAI methods. We found that the proportions of CD8+ T cells, activated NK cells, and follicular helper T cells were significantly higher in the endometria of women with endometriosis than in the endometria of normal controls, while the proportions of M2 macrophages and resting mast cells were significantly lower in the eutopic endometria. In GSE120103 (n = 36), we found that elevated CD8+ T cells in endometriosis increased the risk of infertility (P = 0.0019). The area under the receiver operating characteristic (ROC) curve (AUC) of CD8+ T cells to distinguish fertile and infertile endometriosis was 0.914. In clinical samples (n = 40), we found that the proportions of CD8+ T cells and CD56+ NK cells were significantly higher in the eutopic endometria of women with endometriosis than in the endometria of normal controls, while the proportion of CD163+ macrophages were lower in the eutopic endometria. The AUCs of CD8+ T cells and CD163+ macrophages were 0.727 and 0.833, respectively, which indicated that CD8 and CD163 were potential diagnostic markers for endometriosis. In conclusion, our results demonstrated that increased CD8+ T cells and CD56+ NK cells and decreased CD163+ macrophages within the eutopic endometria of women with endometriosis reveal a proinflammatory feature in the endometrial immune environment and that elevated CD8+ T cells increase the risk of infertility in women with the disease.