Foxp3⁺CD39⁺CD73⁺ regulatory T-cells are decreased in the peripheral blood of women with deep infiltrating endometriosis

Abstract

Endometriosis's pathophysiology remains incompletely understood, with evidence pointing towards a dysregulated immune response. Regulatory T (Treg) cells, pivotal in maintaining self-tolerance, may facilitate the survival of ectopic endometrial cells within the abdominal cavity, thereby contributing to endometriosis development. This study aimed to assess the prevalence of CD39+CD73+ suppressor Treg cell subsets in the peripheral blood of endometriosis patients. This research focuses on the pivotal role of regulatory T-cells (Tregs), which are essential for maintaining immune tolerance and preventing autoimmune diseases. A case-control study was conducted, including 32 women diagnosed with endometriosis and 22 control subjects. The frequency of peripheral blood CD39+CD73+ suppressor Treg cells was quantified using flow cytometry. No significant differences were observed in the frequency of CD3+CD4+CD25High cells (Median [M]: 10.1; Interquartile Range [IQR]: 6.32‒18.3 vs. M: 9.72; IQR: 6.22-19.8) or CD3+CD4+CD25HighCD39+Foxp3+ cells (M: 31.1; IQR: 19.7-44.0 vs. M: 30.55; IQR: 18.5-45.5) between controls and patients. However, a significantly lower frequency of CD3+CD4+CD25HighCD39+CD73+ cells was observed in the endometriosis group compared to controls (M: 1.98; IQR: 0.0377-3.17 vs. M: 2.25; IQR: 0.50-4.08; p = 0.0483), suggesting a reduction in systemic immune tolerance among these patients. This finding highlights the potential role of CD39 and CD73 expression on Treg cells as biomarkers for assessing disease severity and progression. Furthermore, elucidating the mechanisms driving these alterations may unveil new therapeutic strategies to restore immune equilibrium and mitigate endometriosis symptoms.

Keywords
Endometriosis; T Lymphocytes; Regulatory T-cells; Immunology; CD39+CD73+ suppressor Treg cells

Highlights

• Tregs maintain self-tolerance and may allow the survival of ectopic endometrium.

• CD3⁺CD4⁺CD25^High cells were similar between endometriosis and controls.

• CD3⁺CD4⁺CD25^HighCD39⁺Foxp3⁺ cells were similar between endometriosis and controls.

• Foxp3⁺CD39⁺CD73⁺ Tregs are decreased in the blood of women with endometriosis.

• There is a decrease in systemic immune tolerance in patients with endometriosis.