PD-1/PD-L Pathway Potentially Involved in ITP Immunopathogenesis

被引:27
作者
Nie, Mu [1 ]
Liu, Yang [1 ]
Li, Xiu-xiu [1 ]
Min, Ya-nan [2 ,3 ]
Yang, Dan-dan [1 ]
Li, Qiang [1 ]
Feng, Qi [1 ]
Hou, Yu [1 ]
Li, Guo-sheng [1 ]
Sun, Jian-zhi [1 ]
Hou, Ming [1 ,4 ,5 ]
Shi, Yan [1 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Hematol, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China
[2] Karolinska Inst, Dept Med, Stockholm, Sweden
[3] Jining Med Univ, Affiliated Hosp, Dept Hematol, Jining, Shandong, Peoples R China
[4] Shandong Univ, Qilu Hosp, Shandong Prov Key Lab Immunohematol, Jinan, Shandong, Peoples R China
[5] Shandong Univ, Qilu Hosp, Dept Sci & Technol Shandong Prov, Leading Res Grp Sci Innovat, Jinan, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
immune thrombocytopenia; PD-1; PD-L1; PD-L2; T cell; IDIOPATHIC THROMBOCYTOPENIC PURPURA; DEATH-1; PD-1; PATHWAY; PROGRAMMED DEATH-1; T-CELLS; MEDIATED CYTOTOXICITY; INDUCED EXPRESSION; RECEPTOR; TOLERANCE; LIGANDS; LUPUS;
D O I
10.1055/s-0039-1679909
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells turns off autoreactive T cells and induces peripheral tolerance. Aberrant PD-1/PD-L signalling could result in a breakdown of peripheral tolerance and lead to autoimmune diseases. In this study, we detected PD-1 and PD-L expression on T cells and dendritic cells (DCs) in immune thrombocytopenia (ITP) patients with active disease by flow cytometry. The effects of PD-L1-Fc fusion protein (PD-L1-Fc) on T cells and on secretion of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) were detected by flow cytometry and enzyme-linked immunosorbent assay, respectively. Compared with healthy controls, PD-1 expression was significantly increased in CD4(+) T cells and CD8(+) T cells from patients with active ITP. However, PD-L1 expression on monocyte-derived DCs was lower in patients with active ITP than in healthy controls. In vitro assays revealed that PD-L1-Fc increased T cell apoptosis, inhibited activation and proliferation of CD4(+) T cells and CD8(+) T cells and decreased IFN-gamma and IL-2 secretion in patients with active ITP. These results suggest that the aberrant PD-1/PD-L negative co-stimulatory pathway may play a role in ITP. Enhancing PD-1/PD-L signalling might be a promising therapeutic approach for ITP patients by enhancing T cell apoptosis, inhibiting T cell activation and proliferation and reducing secretion of inflammatory factors.
引用
收藏
页码:758 / 765
页数:8
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