Thromb Haemost 2019; 119(05): 758-765
DOI: 10.1055/s-0039-1679909
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

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

Mu Nie*
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Yang Liu*
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Xiu-xiu Li
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Ya-nan Min
2  Department of Medicine, Karolinska Institutet, Stockholm, Sweden
3  Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
,
Dan-dan Yang
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Qiang Li
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Qi Feng
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Yu Hou
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Guo-sheng Li
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Jian-zhi Sun
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
,
Ming Hou
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
4  Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China
5  Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Qilu Hospital, Shandong University, Jinan, China
,
Yan Shi
1  Department of Hematology, Qilu Hospital, Shandong University, Jinan, China
› Author Affiliations
Funding This work was supported by grants from the National Natural Science Foundation of China (81170475, 81470285, 81770114, 81770133, 81470284), Major Research Plan of National Natural Science Foundation of China (91442204), Natural Science Foundation of Shandong Province (ZR2017PH022, ZR2017PH041) and Major Research Plan of Natural Science Foundation of Shandong Province (ZR2016QZ008).
Further Information

Publication History

13 September 2018

10 January 2019

Publication Date:
26 February 2019 (eFirst)

Abstract

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-γ (IFN-γ) 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-γ 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.

Authors' Contributions

M.N. and X.-x.L. performed research, analysed data and wrote the manuscript; Y.L., D.-d.Y., Q.L. and Y.H. performed research; Y.-n.M. and Q.F. performed research and analysed data; G.-s.L. and J.-z.S. analysed data; Y.S. contributed vital new reagents, designed the study and wrote the manuscript; M.H. revised the manuscript; and all authors read and edited the manuscript.


Note

Part of this study was orally presented at the 9th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis, Taipei, Taiwan, China, October 6–9, 2016, and part of this study was presented as a poster at the 60th American Society of Hematology Annual Meeting, San Diego, California, United States, December 1–4, 2018.


* M.N. and Y.L. contributed equally to this study.


Supplementary Material