Involvement of natural killer cells in the pathogenesis of endometriosis in patients with pelvic pain

Abstract

Objectives To detect the involvement of immune cells in the pathogenesis of endometriosis in patients with stable status or pelvic pain. Methods Blood was collected from patients with endometriosis with and without pelvic pain. Natural killer (NK) and Th17 cells were analyzed by flow cytometry, and secretion of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-7) was verified by enzyme-linked immunosorbent assay. We isolated immune cells from blood by density-gradient centrifugation to investigate the expression of functional molecules including sterile alpha motif domain-containing protein 9 (SAMD9), Ral guanine nucleotide dissociation stimulator-like 2 (RGL2), early growth response protein 1, and Akirin2. We also searched the BIOGPS database for protein expression profiles. Results SAMD9 and RGL2 expression levels were significantly upregulated in patients with pelvic pain. Furthermore, lysophosphatidic acid receptor 1 expression was higher in endometrial tissues from patients with pelvic pain, and was mainly localized in stromal and glandular epithelial cells in ectopic lesions. Conclusion NK cells play an important role in the pathogenesis of endometriosis in patients with pelvic pain. Suppressing the cytotoxic activity of NK cells may thus help to reduce the progression of pelvic pain in patients with endometriosis.

Ocular Surface Immune Cell Profiles in Contact Lens–Induced Discomfort

“… 18 The levels of NK cells in the peripheral blood were significantly higher in endometriosis patients with pelvic pain compared with women with stable disease without pelvic pain. 40 In both physiological and pathological conditions, peripheral nociceptive (including pruriceptive) neurons may express a variety of immune-related receptors, such as chemokine receptors and immunoglobulin (Fc) receptors that are usually found on immune cells. 41 Certain ligands such as chemokines and immune complexes may induce abnormal neuronal hyperexcitability and even the discharge of ectopic action potentials, thus producing the sensation of pain, discomfort, or itch in immune-related disease.…”

Association between gene polymorphisms of IL‐12, IL‐12 receptor and IL‐27 and organ involvement in Iranian endometriosis patients

“…Interestingly, we found that the AA genotype of IL‐12B rs3212227 was associated with the decreased risk of uterus involvement in endometriosis patients. The mechanism of this association is not clear; however, as A) IL‐12 is important for NK cell activation and functionality (Zwirner & Ziblat, 2017) B) uterus harbours specific subsets of NK cells (Strunz et al., 2021) C) and recent studies have highlighted the importance of NK cells in the pathogenesis of endometriosis (He et al., 2020; Ścieżyńska et al., 2019), we propose that there might be a link between the aforementioned SNP and NK cell functionality in the context of endometriosis.…”

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

“…Progesterone is an essential hormone that may be given orally or applied topically for pregnancy maintenance [101][102][103]. NK cells do not have receptors for this hormone; however, T cells do [102][103][104]. The factor induced by progesterone, PIBF, generates a tolerogenic TH2 response in the endometrium and consequently may affect NK cell migration and response [105].…”