Phagocyte function of peripheral neutrophil granulocytes and monocytes in endometriosis before and after surgery

Lukács, Luca; Kovács, Ágnes Éva; Pajor, László; Szűcs, Sándor; Kövér, Á.; Lampé, Rudolf

doi:10.1016/j.jogoh.2020.101796

Cited by 13 publications

(11 citation statements)

References 26 publications

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“…Importantly, classical and intermediate monocytes are in lower abundance and pDCs and activated non-classical monocytes are more abundant in blood from women with versus without disease. These findings are in line with a recent study that described decreased phagocytic function of monocytes in blood from patients with endometriosis before surgery, and normalization after lesion removal, compared to controls undergoing surgery but without endometriosis [31]. In addition, proliferation of endometrial cells in vitro from women with endometriosis is significantly enhanced by blood monocytes; whereas, monocytes from healthy patients inhibit their proliferation [32], indicating factors influencing these cells act as enhancers or suppressors of endometriotic lesion development.…”

Section: Discussionsupporting

confidence: 92%

Deep Immunophenotyping Reveals Endometriosis is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood

Vallvé-Juanico

George

Sen

et al. 2022

Preprint

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Background: Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages. Methods: A case-control study was designed. Endometrial biopsies and blood (n=60 total) were obtained from women with (n=20, n=17, respectively) and without (n=14, n=9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed; one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed. Results: The broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91+ macrophages overexpressed SIRPa; (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease. Conclusions: A greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages CD91+ in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.

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Section: Discussionsupporting

confidence: 92%

Deep Immunophenotyping Reveals Endometriosis is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood

Vallvé-Juanico

George

Sen

et al. 2022

Preprint

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“…These two populations are observed in increased numbers within endometrial lesions [23]. However, the phagocyte function of peripheral monocytes and neutrophil granulocytes seem to be decreased and its activity is affected by the presence or removal of endometriotic lesions in women with endometriosis [24].…”

Section: The Role Of Immunocompetent Cells In the Development Of Endo...mentioning

confidence: 99%

The Role of the Immune System in the Development of Endometriosis

Abramiuk

Grywalska

Małkowska

et al. 2022

Cells

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Endometriosis is a chronic disease that affects about 10% of women of reproductive age. It can contribute to pelvic pain, infertility or other conditions such as asthma, cardiovascular disease, breast or ovarian cancer. Research has shown that one of the conditions for the development of endometrial lesions is the dysfunction of the immune system. It appears that immune cells, such as neutrophils, macrophages, NK cells and dendritic cells, may play a specific role in the angiogenesis, growth and invasion of endometriosis cells. Immune cells secrete cytokines and defensins that also affect the endometriosis environment. This review discusses the various components of the immune system that are involved in the formation of endometrial lesions in women.

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“…26,27 Neutrophils contribute to the replacement of EC cells and stimulation of angiogenesis by producing factors, such as IL-6, IL-8, IL-17, vascular endothelial factor (VEGF), and C-X-C motif chemokine ligand 10 (CXCL10) in the peritoneal fluid (PF) and EC lesions. 28 The pathogenesis of the disease can be identified through various features and pathways, including decreased phagocytic activity 29 and apoptosis in neutrophils of women with endometriosis, 30 expression of different transcription factors (TF) from neutrophils in healthy women, 31 as well as the presence of neutrophil extracellu-lar traps (NETs) in the PF of women with endometriosis. 32 Among EC endometrium and eutopic (EU) endometrium, neutrophils do not change significantly.…”

Section: Neutrophilmentioning

confidence: 99%

“…The pathogenesis of the disease can be identified through various features and pathways, including decreased phagocytic activity 29 and apoptosis in neutrophils of women with endometriosis, 30 expression of different transcription factors (TF) from neutrophils in healthy women, 31 as well as the presence of neutrophil extracellular traps (NETs) in the PF of women with endometriosis 32 . Among EC endometrium and eutopic (EU) endometrium, neutrophils do not change significantly.…”

Section: Innate Immune Cells In Endometriosismentioning

confidence: 99%

Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators

Moghaddam

Ansariniya

Seifati

et al. 2022

American J Rep Immunol

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Background Endometriosis is a chronic inflammatory disease associated with the growth and proliferation of endometrial‐like tissues outside the uterus. Although the exact etiology and mechanism of the pathogenesis of the disease have not been fully elucidated, the immune system cells and the mediators produced by them can be named as effective factors in the onset and progression of the disease. Aims We aim to attempt to review studies on the role of the immune system in endometriosis to better understand the pathogenesis of endometriosis. Content Abundant production of inflammatory mediators by neutrophils and macrophages and reduced cytotoxicity of defined cells promote endometriosis at the early stages of the disease. Following an increase in the inflammation of the environment, the body takes compensatory mechanisms to reduce inflammation and establish homeostasis. For this purpose, the body produces remodeling and anti‐inflammatory factors leading to slow conversion of the inflammatory environment into a non‐inflammatory environment with proliferative and immunosuppressive properties. Environmental conditions induce M2 macrophages, TH2 cells, and Tregs differentiation, promoting disease progression by producing angiogenic and immunosuppressive factors. However, the exact molecular mechanism involved in changing inflammatory to non‐inflammatory conditions is not yet fully understood. Implications Due to the common characteristics of endometriotic cells and cancer cells, most potential treatment options for endometriosis have been suggested due to the results of these methods in the treatment of cancer. In this pathway, immune system cells and soluble mediators can be used as targets.

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Phagocyte function of peripheral neutrophil granulocytes and monocytes in endometriosis before and after surgery

Cited by 13 publications

References 26 publications

Deep Immunophenotyping Reveals Endometriosis is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood

Deep Immunophenotyping Reveals Endometriosis is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood

The Role of the Immune System in the Development of Endometriosis

Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators

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