Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells

Joanna Olkowska-Truchanowicz; Alicja Sztokfisz-Ignasiak; Aneta Zwierzchowska; Izabela Janiuk; Filip Dąbrowski; Grażyna Korczak-Kowalska; Ewa Barcz; Katarzyna Bocian; Jacek Malejczyk

doi:10.3390/jcm10173789

Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4⁺CD25^highFOXP3⁺ Treg Cells

J Clin Med. 2021 Aug 25;10(17):3789. doi: 10.3390/jcm10173789.

Authors

Affiliations

¹ Department of Transplantology and Central Tissue Bank, Center of Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland.
² Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland.
³ 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland.
⁴ Department of Obstetrics and Gynecology, Multidisciplinary Hospital Warsaw-Miedzylesie, 04-749 Warsaw, Poland.
⁵ Department of Gynecology and Obstetrics, Medical University of Silesia, 40-055 Katowice, Poland.
⁶ Department of Immunology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
⁷ Laboratory of Experimental Immunology, Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland.

Abstract

Endometriosis is a common gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus. The disease is associated with disturbed local and systemic immunity. It has been reported that the proportion of CD4⁺CD25^highFOXP3⁺ Treg cells may be significantly increased in the peritoneal fluid of patients with endometriosis. Therefore, the aim of our study was to investigate whether the proportions of Treg cells in the peritoneal cavity of patients with endometriosis are related to the chemotactic and stimulatory activity of the local peritoneal milieu. The peritoneal fluid was collected from 13 women with ovarian endometriosis and 12 control women without the disease. T cell populations were analyzed by flow cytometry, cytokines and chemokines were evaluated using the cytometric bead kit, and cell chemotaxis was studied by cell migration assay. We confirmed that the proportions of Treg cells are increased in the peritoneal fluid of women with endometriosis as compared to the control women. Endometriosis was also associated with elevated concentrations of IL-6, IL-10, and TGF-β1/2 as well as CCL20, CXCL8, CXCL9, and CXCL10. We did not reveal any changes in the proportion of peritoneal Th17 cells and concentrations of IL-17A. Peritoneal Treg cells positively correlated with concentrations of TGF-β, IL-10, and CCL20. Endometriotic peritoneal fluid stimulated chemotaxis of both CD4⁺ and Treg cells. This chemotactic activity positively correlated with concentrations of CCL20. CCL20 stimulated the migration of Treg cells, and the chemotactic activity of the endometriotic peritoneal fluid was inhibited by neutralizing anti-CCL20 antibodies. These results imply that increased proportions of the peritoneal Treg cells in women with endometriosis may result from attraction and activation by local chemokines and cytokines, especially CCL20 and TGF-β. Since Treg cells contribute to the immunopathogenesis of endometriosis, their chemotaxis and activation may be considered as a target for therapeutic intervention.

Keywords: CCL20; TGF-β; Th17 cells; chemokines; cytokines; endometriosis; peritoneal fluid; treg cells.

Abstract

Grants and funding