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

Thrombosis and Haemostasis
Mu NieYan Shi

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-...Continue Reading

Citations

Sep 2, 2020·Current Opinion in Hematology·John W SempleRick Kapur
Oct 23, 2019·Frontiers in Immunology·Weiting QinXu Wang
Mar 7, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jian ShouWeihua Xiao
May 2, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yichi XuZhi-Wei Wang
May 27, 2021·Med·Joanna RoopkumarAlok A Khorana

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