Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis

Gogacz, Marek; Winkler, Izabela; Bojarska‐Junak, Agnieszka; Tabarkiewicz, Jacek; Semczuk, Andrzej; Rechberger, Tomasz; Adamiak, Aneta

doi:10.1016/j.jri.2016.04.289

Cited by 74 publications

(74 citation statements)

References 32 publications

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“…In the context of endometriosis, we and others have shown that IL-17A is elevated in the plasma and peritoneal fluid of women with endometriosis compared to controls and that endometriotic lesions produce IL-17 (17,18). T H 17 cells are also elevated in women with endometriosis compared to controls and women in advanced stages of endometriosis have higher numbers of T H 17 cells compared to early stage patients with minimal/mild endometriosis (19)(20)(21). IL-17A is chemotactic for macrophages via its receptor, IL-17RA, and can also induce M2 polarization (22).…”

Section: Introductionmentioning

confidence: 63%

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

et al. 2020

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Endometriosis is a debilitating gynecological disease characterized by the extrauterine presence of endometrial-like tissues located on the peritoneal membrane and organs of the pelvic cavity. Notably, dysfunctional immune activation in women with endometriosis could also contribute to the development of disease. In particular, alternatively activated (M2) peritoneal macrophages are shown to aid peritoneal lesion development by promoting remodeling of extracellular matrix and neovascularization of lesions. However, the stimuli responsible for polarizing M2 macrophages in endometriosis remain elusive. Interleukin-17A (IL-17A) can induce M2 macrophage polarization in other disease models and IL-17A is elevated in the plasma and endometriotic lesions of women with endometriosis. In this study, we investigated whether IL-17A could induce macrophage recruitment and M2 polarization, while promoting endometriotic lesion growth through enhanced vascularization. By utilizing a co-culture of macrophage-like THP-1 cells with an endometriotic epithelial cell line, our in vitro results suggest that IL-17A indirectly induces M2 markers CCL17 and CD206 by interacting with endometriotic epithelial cells. Further, in a syngeneic mouse model of endometriosis, IL-17A treatment increased macrophages in the peritoneum, which were also M2 in phenotype. However, IL-17A treatment did not augment proliferation or vascularization of the lesion in the study time frame. These findings suggest that IL-17A may be a stimulus inducing the pathogenic polarization of macrophages into the M2 phenotype by first acting on the endometriotic lesion itself.

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Section: Introductionmentioning

confidence: 63%

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

et al. 2020

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“…The frequency of Th17 in endometriosis lesions is higher than in that of the normal endometrium, 73 and their high frequency in peritoneal fluid is associated with the increased severity of disease. 80 IL-17a is also described as an aggravator of endometriosis because it exacerbates inflammation and endometriotic cell proliferation. [81][82][83] More research is required to clarify the role of Th17 in disease progression.…”

Section: Th17 and Treg In Endometriosismentioning

confidence: 99%

“…Th17 are one of the helper T cell subsets and they are defined by their production of IL‐17a, a pro‐inflammatory cytokine. The frequency of Th17 in endometriosis lesions is higher than in that of the normal endometrium, and their high frequency in peritoneal fluid is associated with the increased severity of disease . IL‐17a is also described as an aggravator of endometriosis because it exacerbates inflammation and endometriotic cell proliferation .…”

Section: Introductionmentioning

confidence: 99%

Involvement of immune cells in the pathogenesis of endometriosis

Izumi

Koga

Takamura

et al. 2018

J of Obstet and Gynaecol

124

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Endometriosis is characterized by the implantation and growth of endometriotic tissues outside the uterus. It is widely accepted the theory that endometriosis is caused by the implantation of endometrial tissue from retrograde menstruation; however, retrograde menstruation occurs in almost all women and other factors are required for the establishment of endometriosis, such as cell survival, cell invasion, angiogenesis, and cell growth. Immune factors in the local environment may, therefore, contribute to the formation and progression of endometriosis. Current evidence supports the involvement of immune cells in the pathogenesis of endometriosis. Peritoneal neutrophils and macrophages secrete biochemical factors that help endometriotic cell growth and invasion, and angiogenesis. Peritoneal macrophages and NK cells in endometriosis have limited capability of eliminating endometrial cells in the peritoneal cavity. An imbalance of T cell subsets leads to aberrant cytokine secretions and inflammation that results in the growth of endometriosis lesions. It is still uncertain whether these immune cells have a role in the initial cause and/or stimulate actions that enhance disease; however, in either case, modulating the actions of these cells may prevent initiation or disease progression. Further studies are needed to deepen the understanding of the pathology of endometriosis and to develop novel management approaches of benefit to women suffering from this disease.

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“…In addition to innate immunity, cells from adaptive immunity also play a role in endometriosis (Riccio et al, 2018). Activation of CD4 + T cells has been described with an imbalance toward a T helper 2 (Th2) phenotype that drives the fibrosis of lesions (Chen et al, 2016), and a combined increase in T helper 17 cells maintains the inflammatory process (Gogacz et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice

et al. 2019

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STUDY QUESTION What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER Skewing activated B cells toward regulatory B cells (Bregs) by Bruton’s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.

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Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis

Cited by 74 publications

References 32 publications

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

Involvement of immune cells in the pathogenesis of endometriosis

B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice

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