Problem: The lymphatic vasculature controls leukocytes trafficking and limits the adaptive immune response. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophysiology. Especially, the dysfunction of regulatory T cells (Treg) at the maternal-fetal interface may be one of the causes of severe PE. In particular, activation of Tregs to obtain immune tolerance requires adequate antigen presentation through the lymphatic system. We hypothesized that impaired lymphangiogenesis and imbalanced Tregs at the maternal-fetal interface are associated with the pathophysiology of severe PE. However, the current research addressing this hypothesis is limited. Therefore, to compare differences in lymphangiogenesis in severe PE and normal conditions, we aimed to examine the location of lymphatics at the maternal-fetal interface and to investigate the association between lymphangiogenesis and Tregs in severe PE. Method of Study: We obtained entire uterus from normal pregnant mice. Placental and fetal membranes, including decidua, were obtained from 10 pregnant women with severe PE and 10 gestational age-matched controls. Immunohistochemistry for LYVE1 was used to localize the distribution of lymphatic vessels and CD4, CD25, and FOXP3 for Treg. Results: LYVE1-positive vessels were present in the uterine wall of mice. LYVE1-positive lymphatic vessels were localized on the human decidua. Tubular lymphatics were abundant in the control decidua, but significantly reduced in severe PE. Furthermore, lymphatic vessel density correlated with the number of decidual Tregs. Conclusion: Abnormal decidual lymphangiogenesis is associated with reduced numbers of decidual Tregs in severe PE.
Bibliographical noteFunding Information:
Funding information The Basic Science Research Program, through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education (NRF-2016R1D1A1B03933337 and NRF-2017R1D1A1B03029081), supported this research. The authors would like to thank Professor Gil, Mor (Department of Obstetrics Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA) for all his advice, guidance, and encouragement. The authors would like to thank Dong-Su Jang, MFA, (Medical Illustrator, Medical Research Supporting Section, Yonsei University College of Medicine, Seoul, Korea) for help with the illustrations.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Reproductive Medicine
- Obstetrics and Gynaecology