Involvement of immune cells in the pathogenesis of endometriosis

Izumi, Gentaro; Koga, Kaori; Takamura, Masashi; Makabe, Tomoko; Satake, Erina; Takeuchi, Arisa; Taguchi, Ayumi; Urata, Yoko; Fujii, Tomoyuki; Osuga, Yutaka

doi:10.1111/jog.13559

Cited by 135 publications

(90 citation statements)

References 91 publications

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“…It is well known that the relationship between endometriosis and the immune system is intimate [64][65][66] . Macrophages, for example, have long been known to act as important cells within the normal eutopic endometrium 67 and in the etiopathogenesis of endometriosis, where they are potentially responsible for survival, neovascularization, the growth of ectopic lesions 68 , and the formation of endometriomas 69 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Poli-Neto

Meola

Silva

et al. 2020

Sci Rep

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Eutopic endometrium appears to be crucial for endometriosis development. Despite of the evident importance, data regarding the cellular microenvironment remain unclear. Our objective was to explore the tissue microenvironment heterogeneity, transcripts, and pathways that are enriched in all phases of the menstrual cycle by analysing publicly deposited data derived from whole transcriptome microarrays of eutopic endometria of women with and without endometriosis. A meta-analysis of the transcriptome microarrays was performed using raw data available from a public database. Eligibility criteria included eutopic endometrium samples from women with endometriosis and healthy controls without any pathological condition reported the presence of an adequately reported normal menstrual phase, and samples containing both glandular and stromal components. Raw data were processed using a robust multiarray average method to provide background correction, normalisation, and summarisation. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Cellular tissue heterogeneity was inferred using the xCell package. Differentially expressed genes were identified based on a 5% adjusted p value and a 2.0-fold change. Pathways were identified by functional enrichment based on the Molecular Signatures Database, a p value of < 5%, and an FDR q value of ≤ 25%. Genes that were more frequently found in pathways were identified using leading edge analysis. In a manner independent of cycle phase, the subpopulations of activated dendritic cells, CD4 T effector memory phenotype cells, eosinophils, macrophages M1, and natural killer T cells (NKT) were all higher in stage I-II endometriosis compared to those in healthy controls. The subpopulations of M2 macrophages and natural killer T cells were elevated in eutopic endometriums from women with stage III-IV endometriosis, and smooth muscle cells were always more prevalent in healthy eutopic endometriums. Among the differently expressed genes, FOS, FOSB, JUNB, and EGR1 were the most frequently mapped within the interaction networks, and this was independent of stage and cycle phase. The enriched pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial mesenchymal transition. PI3K AKT mTOR, TGF signalling, and interferon alpha/gamma responses were enriched exclusively in stage III-IV endometriosis. The cellular microenvironments and immune cell profiles were different between eutopic endometriums from women with stage I-II and stage III-IV endometriosis, and these differences were independent of the hormonal milieu. Specifically, a pro-inflammatory profile was predominant in stage I-II endometriosis, and M1-M2 polarization into eutopic endometrium may be crucial for the progression of the disease. The higher prevalence of NKT cells in eutopic endometriums from women with endometriosis that

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Section: Discussionmentioning

confidence: 99%

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Poli-Neto

Meola

Silva

et al. 2020

Sci Rep

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“…These models allowed us to study the impact of hypo-, hyper-and euthyroidism, as well as thyroid autoimmunity, on endometriosis evolution. Endometriosis is an inflammatory disease (1,2,6), characterized by an important leukocytic infiltration in the ectopic endometrium (36,37). The presence of high levels of thyroid antigens like TG, thyroid hormones, or TSHR in endometriotic cells may favor their exposure to the immune system in an immunostimulant environment that could trigger the breach of tolerance and the autoimmune reaction toward the thyroid autoantigens.…”

Section: Discussionmentioning

confidence: 99%

Role of thyroid dysimmunity and thyroid hormones in endometriosis

Peyneau

Kavian

Chouzenoux

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Endometriosis is characterized by the presence of ectopic endometrial cells outside the uterine cavity. Thyroid autoimmunity has been associated with endometriosis. This work investigated the potential pathophysiological link between endometriosis and thyroid disorders. Transcripts and proteins involved in thyroid metabolism are dysregulated in eutopic and ectopic endometrium of endometriotic patients, leading to resistance of ectopic endometrium to triiodothyronine (T3) action and local accumulation of thyroxine (T4). Thyroid-stimulating hormone (TSH) acts as a proliferative and prooxidative hormone on all endometria of endometriosis patients and controls, whereas T3 and T4 act to specifically increase ectopic endometrial cell proliferation and reactive oxygen species (ROS) production. Mouse studies confirmed the data gained in vitro since endometriotic implants were found to be bigger when thyroid hormones increased. A retrospective analysis of endometriosis patients with or without a thyroid disorder revealed an increased chronic pelvic pain and disease score in endometriotic patients with a thyroid disorder. thyroid | thyroid hormones | endometriosis | oxidative stress | autoimmunity

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“…Other studies report that phagocytosis inactivation by PGE2 trough CD36 inhibition is mediated by the EP-2. On the other hand, cytokines secretion activity by these cells is increased; for example, IL-8, IL-10, and tumor necrosis factor (TNF)-α are found in peritoneal fluid of endometriosis patients at greater levels than fertile women (66); thus, macrophages could promote and sustain an inflammatory environment required for endometriosis progress (67).…”

Section: Alteration Of Immune Cell Functionmentioning

confidence: 99%

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

et al. 2020

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Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue (glands and stroma) outside the uterus, mainly in the peritoneal cavity, ovaries, and intestines. This condition shows estrogen dependency and progesterone resistance, and it has been associated with chronic inflammation, severe pain, and infertility, which negatively affect the quality of life in reproductive women. The molecular mechanisms involved in the pathogenesis of endometriosis are not completely understood; however, inflammation plays a key role in the pathophysiology of the disease, mainly by altering the function of immune cells (macrophages, natural killer, and T cells) and increasing levels of pro-inflammatory mediators in the peritoneal cavity, endometrium, and blood. These immune alterations inhibit apoptotic pathways and promote adhesion and proliferation of endometriotic cells, as well as angiogenesis and neurogenesis in endometriotic lesions. It has been demonstrated that hormonal alterations in endometriosis are related to the inflammatory unbalance in this disease. Particularly, steroid hormones (mainly estradiol) promote the expression and release of pro-inflammatory factors. Excessive inflammation in endometriosis contributes to changes of hormonal regulation by modulating sex steroid receptors expression and increasing aromatase activity. In addition, dysregulation of the inflammasome pathway, mediated by an alteration of cellular responses to steroid hormones, participates in disease progression through preventing cell death, promoting adhesion, invasion, and cell proliferation. Furthermore, inflammation is involved in endometriosis-associated infertility, which alters endometrium receptivity by impairing biochemical responses and decidualization. The purpose of this review is to present current research about the role of inflammasome in the pathogenesis of endometriosis as well as the molecular role of sex hormones in the inflammatory responses in endometriosis.

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Involvement of immune cells in the pathogenesis of endometriosis

Cited by 135 publications

References 91 publications

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Role of thyroid dysimmunity and thyroid hormones in endometriosis

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

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