Abstract

Endometriosis is a gynecological condition that is associated with chronic pelvic inflammation, pain, and infertility. Although substantial evidence supports that immunological alterations contribute to its pathogenesis and we previously posed a pivotal role of Galectin-9 (Gal-9) in this disorder, the involvement of the TIM-3/Gal-9 pathway in the development of endometriosis-associated immunological abnormalities is not yet known. In the present study, multicolor flow cytometry was used to compare the immunophenotype and cell surface expression of TIM-3 and Gal-9 molecules on peripheral blood (PB) and peritoneal fluid (PF) lymphocytes of women with and without endometriosis. We found an altered distribution of different lymphocyte subpopulations, a markedly decreased TIM-3 labeling on all T and NK subsets and a significantly increased Gal-9 positivity on peripheral CD4+ T and Treg cells of the affected cohort. Furthermore, a significantly increased TIM-3 expression on CD4+T-cells and elevated Gal-9 labeling on all T and NK subsets was also revealed in the PF of the examined patients. In conclusion, our results suggest a persistent activation and disturbed TIM-3/Gal-9-dependent regulatory function in endometriosis, which may be involved in the impaired immune surveillance mechanisms, promotes the survival of ectopic lesions, and aids the evolution of reproductive failures in endometriosis.

Highlights

  • Endometriosis is a common chronic, progressive gynecologic condition that influences the quality of life and can lead to infertility

  • As the exact immunophenotypic composition of the peripheral blood (PB) and peritoneal fluid (PF) immune cell populations in endometriosis were not yet characterized by our Research Team and previous literature data provided inconsistent results, our first aim was to determine the distribution of different T and natural killer (NK) cells in the peripheral blood mononuclear cell (PBMC) subsets of non-endometriotic (NE) control and endometriosis (E)-affected women and in the peritoneal fluid leukocytes (PTL) of the examined patients

  • We detected a significantly increased T-cell immunoglobulin and mucin domain-3 (TIM-3) expression by CD8+ T cells in the PF of women with endometriosis compared to the periphery

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Summary

Introduction

Endometriosis is a common chronic, progressive gynecologic condition that influences the quality of life and can lead to infertility. This complex, estrogen-dependent neuroimmunoendocrine disorder affects 3–10% of women in their reproductive years and 20–50% of women with infertility [1]. Its medical treatment is mainly based on surgery and/or ovarian suppressive agents that could be effective in the temporary relief of symptoms and infertility. Still, up to this day, no treatment is available to cure the disease [3]

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