PD-1/PD-L1 regulates Treg differentiation in pregnancy-induced hypertension

• Published in: Brazilian journal of medical and biological research Vol. 51; no. 8; p. e7334
• Main Authors: Jiang, Lai, Tang, Chaoliang, Gong, Yanping, Liu, Yujie, Rao, Jie, Chen, Suyu, Qu, Wanjun, Wu, Dabao, Lei, Lei, Chen, Ling
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.01.2018; Revista Brasileira de Pesquisas Medicas; Associação Brasileira de Divulgação Científica
• Subjects: Apoptosis; B7-H1 Antigen - metabolism; BIOLOGY; Blotting, Western; Care and treatment; Case-Control Studies; CD25 antigen; CD4 antigen; Cell death; Cell differentiation; Cellular proteins; Development and progression; Differentiation; Enzyme-Linked Immunosorbent Assay; Female; Fetuses; Flow cytometry; Foxp3; Foxp3 protein; Gene expression; Genetic aspects; Gestational hypertension; Health aspects; Humans; Hypertension; Hypertension, Pregnancy-Induced - metabolism; Interleukin 10; Interleukin-10 - metabolism; Interleukins - metabolism; Leukocytes (mononuclear); Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - metabolism; Lymphocytes T; MEDICINE, RESEARCH & EXPERIMENTAL; Monoclonal antibodies; Morbidity; PD-1 protein; PD-1/PD-L1; PD-L1 protein; Peripheral blood mononuclear cells; PIH; Pregnancy; Real-Time Polymerase Chain Reaction; Serum levels; T cells; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta - metabolism; Treg; Foxp3; Differentiation; PD-1/PD-L1; PIH; Treg
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431x20187334

Pregnancy-induced hypertension (PIH) causes significant maternal and fetal morbidity and mortality. A decreased number of regulatory T (Treg) cells is associated with the pathogenesis of PIH. The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical to normal pregnancy (NP) by promoting Treg cell development. However, the relationship between PD-1/PD-L1 and Treg differentiation in PIH has not been fully elucidated. In this study, venous blood was obtained from 20 NP and 58 PIH patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. The levels of Treg-related cytokines (TGF-β, IL-10, and IL-35) in serum and PBMCs were measured by ELISA. The percentage of Treg cells in PBMCs was assessed by flow cytometry. The mRNA levels of Treg-specific transcription factor Foxp3 in PBMCs, and PD-1 and PD-L1 in Treg cells were detected by qRT-PCR. The protein levels of PD-1 and PD-L1 in Treg cells were evaluated by western blot. The serum levels of TGF-β, IL-10, IL-35, and Foxp3 mRNA expression and CD4+CD25+ Treg cell percentage in PBMCs were decreased in PIH. Furthermore, a significant increase of PD-1 in Treg cells was found in PIH compared with NP. In addition, PD-L1 Fc, an activator of PD-1/PD-L1 pathway, increased Treg cell percentage, enhanced Foxp3 mRNA expression, and elevated levels of TGF-β, IL-10, and IL-35 in PBMCs. However, anti-PD-L1 mAb exerted a reverse effect. These findings revealed that PD-L1 Fc had a favorable effect on Treg cell differentiation, indicating a potential therapeutic value of PD-1/PD-L1 pathway for PIH treatment.