title: Contributions of PD-1/PD-L1 pathway to interactions of myeloid DCs with T cells in atherosclerosis.
abstract: Although inflammatory cells contribute to immunopathogenesis of atherosclerosis, underlying molecular mechanisms remain largely undefined. Recently, it has been demonstrated in mouse model that Programmed death-1 (PD-1)/PD-1 ligand (PD-L) pathway plays a critical role in proatherogenic immune responses. Here we examined the expression of PD-1 and PD-L1 on peripheral blood mononuclear cells by flow cytometry in 76 patients with coronary artery disease (CAD), and 25 healthy volunteers. The expression of PD-1 and PD-L1 is significantly down-regulated on T cells and myeloid dendritic cells (mDCs) in CAD patients than in healthy individuals, respectively. More importantly, we found that decreased PD-L1 expression on mDCs is related with the increased T cell immune responses in CAD patients. In addition, stimulation of PD-L1 expression in vitro could attenuate the stimulatory ability on allogeneic T cell proliferation and its cytokine production, including IFN-gamma and IL-2, and also influence the production of IL-10 and IL-12 by mDCs. Taken together, we can draw a conclusion that PD-1/PD-L1 pathway plays a key role in the regulation of proatherogenic T cell immunity by intervening antigen presenting cell (APC)-dependent T cell activation, which associates with pro-inflammatory or anti-inflammatory cytokine production, and further studies need gain insight into that this pathway represents a strategy of immunotherapy for atherosclerosis.
authors.affiliation: Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Baqiao District, Xi'an 710038, P R China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.forename: Fujun
authors.initials: F
authors.lastname: Shang
authors.forename: Jiuping
authors.initials: J
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiongtao
authors.initials: X
authors.lastname: Liu
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Qiangsun
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism*; D060890:B7-H1 Antigen; D016022:Case-Control Studies; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016898:Interferon-alpha; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor