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PD‐1/PD‐L1 expression on CD4+ T cells and myeloid DCs correlates with the immune pathogenesis of atrial fibrillation
Authors:Li Liu  Qiangsun Zheng  Jun Lee  Zhiqiang Ma  Qiming Zhu  Zhiquan Wang
Affiliation:1. Department of Cardiology of Tangdu Hospital, Fourth Military Medical University, Xi'an, China;2. Department of Cardiology of PLA 161 Hospital, Wuhan, China
Abstract:Although immuno‐inflammatory response contributes to pathogenesis of AF, molecular and cellular mechanism in this process remains poorly understood. Recently, increasing evidence suggests that Programmed death‐1 (PD‐1)/PD‐1 ligand (PD‐L) pathway may be a potential pathway participating in AF pathogenesis. In this study, we detected the PD‐1 and PD‐L1, 2 expression on peripheral blood function cells by flow cytometry in 91 atrial fibrillation (AF) patients and 35 healthy volunteers. The expression of PD‐1 on CD4+ T cells and PD‐L1 on myeloid dendritic cells (mDCs) in AF patients is significantly down‐regulated compared with healthy volunteers. In addition, the extent of PD‐1/PD‐L1 down‐regulation is closely related with AF burden. More importantly, Allogeneic mixed leukocyte reactions (MLR) shows that the mDCs PD‐L1 down‐regulation is associated with increased T cell (CD4+ and CD8+) proliferation, increased type 1 effector cytokines (IL‐2 and IFN‐γ) secretion, and decreased type 2 effector cytokine (IL‐10) secretion. Then, PD‐L1 up‐regulation by the stimulation of IFN‐α can significantly convert this representation. Collectively, our report suggest that T(CD4+)/mDCs‐associated PD‐1/PD‐L1 pathway plays a key role in AF immune regulation. PD‐1/PD‐L1 down‐regulation in AF patients promotes T cells function and may contribute to AF pathogenesis.
Keywords:Programmed death‐1  programmed death‐ligand 1  atrial fibrillation  myloid dendritic cell
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