Kyle S Wiley, Laura E Martínez, Daylon Kwon, Delaney A Knorr, Marta Epeldegui, Molly M Fox
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引用次数: 0
Abstract
Problem: Regulatory B-cells (Bregs, CD19+CD24hiCD38hi) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4+CD25hiCD127loFoxP3+) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD-L1-expressing Bregs correlated with Tregs and cytokines during pregnancy.
Method: Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks' gestation. Participants were age ≥ 18, self-identified as Latina/Hispanic, and N = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4+ T-cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD-L1+ Bregs from total B-cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform.
Results: Bregs positively correlated with pro-inflammatory cytokine interleukin (IL)-6. PD-L1+ Bregs positively correlated with T-cell suppressive cytokine IL-10. PD-L1+ Bregs negatively correlated with Tregs and Helios+, CTLA-4+, PD-1+, TIGIT+, and TIM3+ Tregs. For primigravida, PD-L1+ Bregs correlated positively with IL-10 and negatively with Helios+ and TIGIT+ Tregs. For multigravida, PD-L1+ Bregs correlated positively with IL-8 and negatively with Helios+, CTLA-4+, PD-1+, and TIGIT+ Tregs.
Conclusions: This study provides insight into the immunosuppressive role of Bregs and PD-L1+ Bregs during human pregnancy. Our results suggest that PD-L1+ Bregs can employ suppressive mechanisms to limit pro-inflammatory responses in primigravida.
期刊介绍:
The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.