Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis

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.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0325-2) contains supplementary material, which is available to authorized users.

CD4+/CD8+ mucosa-associated invariant T cells foster the development of endometriosis: a pilot study

“…An area of great interest in endometriosis is soaring in immunological activity and its function in development of this condition [6, 9, 10, 12]. The endometriosis-associated immunological reactions were well reported in previous studies indicating the abnormalities in the frequency and function of T cells and their associated cytokines [9, 10, 20].…”

“…Many reports have indicated that the process of endometriosis is related to a dysregulation of the host immune and some researchers even consider EMS to be an autoimmune disorder [5–12]. On one hand, some studies have been focused on downregulation of anti-endometrial implants cells, such as NK cells, CD4 + /CD8 + T cells, B cells and so on [5–8], on the other hand, some studies demonstrated that increased immunosuppressive cells could promote the progression of endometriosis, such as Tregs (regulatory T cells), TH2 (T helper) cells and even MDSCs (myeloid derived suppressor cells), which have been suggested recently to promote the implantation of endometrial tissue [13, 14].…”

“…It has been known that MAIT cells take part in both innate and adaptive immune response and can be found in peripheral blood and other tissues [18, 19]. However, till now there is no study about the relationship between MAIT cells and EMS, even though other kinds of T cells have been fully studied, such as TH17, TH1, TH2 and so on [10, 12, 20, 21]. In humans, MAIT cells have been defined as CD3 + CD161 + Vα7.2 + cells.…”

Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases

“…The discrepancy may result from differences in patient selection, namely the patients with early or advanced endometriosis. Most studies suggest the proportion of Tregs is significantly increased in peritoneal fluid from women with endometriosis compared with control women (157,158,161). One study reported that the number of Tregs was increased in the peritoneal fluid and decreased in the peripheral blood, and another study found the number of Tregs was higher in peritoneal fluid than in peripheral blood, both indicating that active translocation of Tregs occurs from circulation to the local peritoneal cavity (158,162).…”

Brassica Bioactives Could Ameliorate the Chronic Inflammatory Condition of Endometriosis

“…On the other hand, dysfunctional natural killer (NK) cells [ 59 ] that express a higher number of KIR (killing inhibitory receptors) [ 60 ] and a lower level of KAR (killing activating receptors), could play a role in the unsuitable activation and polarization of macrophages by inhibiting their phagocytic capacity and the expression of scavenger receptors [ 61 ]. Furthermore, these NK cells induce the activation of T regulatory (Treg) lymphocytes, whose inhibitory activity would allow endometrial cells to escape from local immune surveillance [ 62 , 63 , 64 , 65 , 66 ]. Additionally, it has been described that the number of peritoneal Myeloid-Derived Suppressor Cells (MDSCs) rapidly increases in the presence of endometrial tissue, thus contributing to the inhibited immune response [ 48 , 67 ].…”