Abstract
BackgroundEndometriosis is a known cause of infertility. Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-β (TGF-β) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-β is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis.MethodsPB and PF were collected from 28 women with laparoscopically and histopathologically diagnosed endometriosis and 20 disease-free women who were subjected to laparoscopic surgery. Three subpopulations of CD4+ T lymphocytes (CD45RA+FoxP3low resting Tregs, CD45RA−FoxP3high effector Tregs, and CD45RA−FoxP3low non-Tregs) and CD11b+ mononuclear cells expressing LAP were analyzed by flow cytometry using specific monoclonal antibodies.ResultsProportions of suppressive Tregs (resting and effector Tregs) were significantly higher in the PF samples of patients with endometriosis than in those of control women (P = 0.02 and P < 0.01, respectively) but did not differ between the PB samples of patients and controls. The percentage of CD11b+LAP+ macrophages was significantly lower in PF samples of patients with endometriosis than in those of controls (P < 0.01) but was not altered in the PB samples.ConclusionProportions of suppressive Tregs and LAP+ macrophages are altered locally in the PF of endometriosis patients.
Highlights
Endometriosis is a known cause of infertility
FACS analysis revealed that the frequencies of CD45RA+FoxP3low resting Regulatory T cells (Tregs) (rTregs) and CD45RA−FoxP3high effector Tregs (eTregs) in the peritoneal fluid (PF) were significantly higher in the endometriosis group than in the control group [medians: 0.25% (P = 0.02) and 1.7% (P < 0.01), respectively]; these did not differ between the two groups in the peripheral blood (PB) [median rTregs: 1.4% and 1.9%, P = 0.31; median eTregs: 0.70% and 0.90%, P = 0.29] (Fig. 2a and b)
There were no significant differences in non-Tregs between patients and controls in either the PB or PF (Fig. 2c)
Summary
Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-β (TGF-β) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-β is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis. In humans, conflicting results have been obtained regarding whether populations of Tregs in the peritoneal fluid (PF) or peripheral blood (PB) differ significantly between patients with endometriosis and controls [8,9,10]. The association between endometriosis and Treg subpopulations has not been well studied. In this study, we focused on assessing the association of each Treg subpopulation with endometriosis
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