CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis

Olkowska-Truchanowicz, Joanna; Bocian, Katarzyna; Maksym, Radosław; Białoszewska, Agata; Włodarczyk, D; Baranowski, Włodzimierz; Ząbek, Jakub; Korczak-Kowalska, G; Malejczyk, Jacek

doi:10.1093/humrep/des346

Cited by 107 publications

(71 citation statements)

References 31 publications

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“…Disturbance of T reg cells, which are responsible for self-tolerance, maintenance of immune homeostasis, and immunosuppressive functions, 22 aggravates the condition of endometriosis. In this study, we have demonstrated not only that the percentage of T reg cells in the peritoneal fluid of endometriosis patients higher than that in healthy women, which is consistent with results of previous published studies, 23 but also that the augmentation of T reg cell percentage, especially that of TGF- β 1 + T reg cells, occurs in parallel with endometriosis exacerbation. This suggests that the detection of peritoneal T reg cells may be used as an indicator to assess the severity of endometriosis.…”

Section: Discussionsupporting

confidence: 92%

“…One is homing of peripheral T reg cells to the peritoneal fluid as the percentage of T reg cells decreases in the peripheral blood of EMS patients. 23 The second is that local naive T cells differentiate into T reg cells under the influence of various factors involved; and the third is self-proliferation of local T reg cells. In fact, all of these assumptions may be involved in the increase of peritoneal T reg cell percentage in endometriosis.…”

Section: Discussionmentioning

confidence: 99%

“…27 Subsequent studies revealed that IDO1 has multiple immunological functions, such as suppressing T-cell responses, regulating functions of T reg cells, 14 and promoting immune tolerance. 15 Evidence of higher IDO1 expression in ectopic ESCs than in normal ESCs 6 and high percentage of peritoneal T reg cells in endometriosis 23 demonstrates that IDO1 may play an important role in inducing the differentiation of T reg cells in the ectopic lesion, which is a probable reason for excessive T reg cells in the peritoneal fluid of patients with endometriosis.…”

Section: Discussionmentioning

confidence: 99%

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1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

et al. 2016

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Foxp3+ regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of Treg cells, mainly IL-10+ Treg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated Treg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of Treg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for Treg differentiation in the ectopic lesion, especially that for CD4high Treg. Therefore, MRC2-silenced ESCs-educated Treg manifested a stronger suppressive function in vitro. Consistently, the percentage of Treg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of Treg and is involved in the development of endometriosis. Thus, blockage of IDO1 in the ectopic lesion, which does not influence physiological functions of estrogen, may be considered a potential therapy for endometriosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

et al. 2016

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“…Treg is another subset of helper T cells and they are known to maintain immunological tolerance. 66 Many studies have shown that Treg are increased in the peritoneal cavity of endometriosis patients [84][85][86][87] ; however, two studies did not find a significant difference. 73,88 In a mouse study, the inhibition of Treg induction (differentiation) reduced the number and weight of endometriotic lesions.…”

Section: Th17 and Treg In Endometriosismentioning

confidence: 98%

Involvement of immune cells in the pathogenesis of endometriosis

Izumi

Koga

Takamura

et al. 2018

J of Obstet and Gynaecol

139

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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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“…One study found increased Treg cells in the peritoneal fl uid and decreased levels in the peripheral blood of women with endometriosis compared to controls without endometriosis. The authors suggest a possible shift from the peripheral blood to the affected tissue as a compensatory method to modulate infl ammation [ 85 ]. Treg cell abnormalities, such as polymorphisms of FOXP3 gene and increased levels of transcriptional factors for FOXP3, have been found in endometriotic lesions [ 86 , 87 ].…”

Section: Immunologymentioning

confidence: 99%

Endometriosis and Cancer: Is There an Association?

Vega

Soto

Goldberg

2015

Biennial Review of Infertility

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CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis

Abstract: This study was supported by 1M15/N/2011 and NK1W grants from the I Faculty of Medicine, Warsaw Medical University. None of the authors has any competing interests to declare.

Cited by 107 publications

References 31 publications

1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

Involvement of immune cells in the pathogenesis of endometriosis

Endometriosis and Cancer: Is There an Association?

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