Olkowska-Truchanowicz Joanna, Sztokfisz-Ignasiak Alicja, Zwierzchowska Aneta, Janiuk Izabela, Dąbrowski Filip, Korczak-Kowalska Grażyna, Barcz Ewa, Bocian Katarzyna, Malejczyk Jacek
Department of Transplantology and Central Tissue Bank, Center of Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland.
Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland.
J Clin Med. 2021 Aug 25;10(17):3789. doi: 10.3390/jcm10173789.
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 CD4CD25FOXP3 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.
子宫内膜异位症是一种常见的妇科疾病，其特征是子宫外存在类似子宫内膜的组织。该疾病与局部和全身免疫紊乱有关。据报道，子宫内膜异位症患者腹腔液中CD4CD25FOXP3调节性T细胞（Treg细胞）的比例可能显著增加。因此，我们研究的目的是调查子宫内膜异位症患者腹腔中Treg细胞的比例是否与局部腹腔环境的趋化和刺激活性相关。从13名患有卵巢子宫内膜异位症的女性和12名未患该疾病的对照女性中收集腹腔液。通过流式细胞术分析T细胞群体，使用细胞计数珠试剂盒评估细胞因子和趋化因子，并通过细胞迁移试验研究细胞趋化性。我们证实，与对照女性相比，子宫内膜异位症女性腹腔液中Treg细胞的比例增加。子宫内膜异位症还与白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、转化生长因子-β1/2（TGF-β1/2）以及CC趋化因子配体20（CCL20）、CXC趋化因子配体8（CXCL8）、CXC趋化因子配体9（CXCL9）和CXC趋化因子配体（CXCL10）浓度升高有关。我们未发现腹腔辅助性T细胞17（Th17细胞）比例和IL-17A浓度有任何变化。腹腔Treg细胞与TGF-β、IL-10和CCL20浓度呈正相关。子宫内膜异位症腹腔液刺激CD4细胞和Treg细胞的趋化性。这种趋化活性与CCL20浓度呈正相关。CCL20刺激Treg细胞的迁移，并且中和抗CCL20抗体可抑制子宫内膜异位症腹腔液的趋化活性。这些结果表明，子宫内膜异位症女性腹腔Treg细胞比例增加可能是由局部趋化因子和细胞因子，尤其是CCL20和TGF-β的吸引和激活所致。由于Treg细胞参与子宫内膜异位症的免疫发病机制，它们的趋化性和激活可被视为治疗干预的靶点。
