Toll-Like Receptor 2 Expression as a New Hallmark of Advanced Endometriosis

Sobstyl, Małgorzata; Niedźwiedzka-Rystwej, Paulina; Grywalska, Ewelina; Korona-Głowniak, Izabela; Sobstyl, Anna; Bednarek, Wiesława; Roliński, Jacek

doi:10.3390/cells9081813

Cited by 12 publications

(4 citation statements)

References 62 publications

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“…A significant number of papers did not consider the menstrual cycle phase in their analysis. Investigators identified comparable findings with no difference in CD8 T cell proportions among leukocytes between endometriosis and control group (29.3 ± 5.5 vs 30.2 ± 4.9, respectively) and no difference in CD4/CD8 ratio (1.4 (0.73–2.7) vs 1.3 (0.93–4.5), respectively) ( 49 ). Interestingly, no difference was observed even when they compared CD8 T rates and CD4/CD8 ratio between different disease stages.…”

Section: Resultsmentioning

confidence: 96%

The role of CD8+ T cells in endometriosis: a systematic review

Kisovar¹,

Becker²,

Granne³

et al. 2023

Front. Immunol.

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BackgroundEndometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).MethodsFour databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.Results28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.ConclusionLiterature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.Systematic Review RegistrationPROSPERO identifier CRD42021233304

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Section: Resultsmentioning

confidence: 96%

The role of CD8+ T cells in endometriosis: a systematic review

Kisovar¹,

Becker²,

Granne³

et al. 2023

Front. Immunol.

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“…Notably, TLR-2, which is essential in the innate immune system, was upregulated in the myeloid dendritic cells and B cells in patients with endometriosis. TLR-2 has been proposed as a potential noninvasive biomarker ( 168 ).…”

Section: The Effect Of Regulating the Immune Microenvironment Of Endo...mentioning

confidence: 99%

Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives

Chen

Liu²,

Zhong³

et al. 2023

Front. Immunol.

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Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.

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“…TLR2 plays a role in bacterial infections and the innate immune system. Its expression has been assessed in endometriosis patients, but further research is needed to understand its specific involvement [ 71 ]. Overall, more studies are needed to explore the presence and potential use of TLRs as biomarkers for the early detection of endometriosis.…”

Section: The Importance Of Disorders Of Immune Homeostasis In the Pat...mentioning

confidence: 99%

How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis

Sobstyl

Chałupnik

Mertowska

et al. 2023

IJMS

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Microorganisms inhabiting the human body play an extremely key role in its proper functioning, as well as in the development of the immune system, which, by maintaining the immune balance, allows you to enjoy health. Dysbiosis of the intestinal microbiota, or in the oral cavity or reproductive tract, understood as a change in the number and diversity of all microorganisms inhabiting them, may correlate with the development of many diseases, including endometriosis, as researchers have emphasized. Endometriosis is an inflammatory, estrogen-dependent gynecological condition defined by the growth of endometrial cells outside the uterine cavity. Deregulation of immune homeostasis resulting from microbiological disorders may generate chronic inflammation, thus creating an environment conducive to the increased adhesion and angiogenesis involved in the development of endometriosis. In addition, research in recent years has implicated bacterial contamination and immune activation, reduced gastrointestinal function by cytokines, altered estrogen metabolism and signaling, and abnormal progenitor and stem cell homeostasis, in the pathogenesis of endometriosis. The aim of this review was to present the influence of intestinal, oral and genital microbiota dysbiosis in the metabolic regulation and immunopathogenesis of endometriosis.

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Toll-Like Receptor 2 Expression as a New Hallmark of Advanced Endometriosis

Cited by 12 publications

References 62 publications

The role of CD8+ T cells in endometriosis: a systematic review

The role of CD8+ T cells in endometriosis: a systematic review

Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives

How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis

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