title: Programmed Death Ligand 1 Plays a Neuroprotective Role in Experimental Autoimmune Neuritis by Controlling Peripheral Nervous System Inflammation of Rats.
abstract: Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages. In this study, we investigated the effects of PD-L1 in EAN rats. For preventative and therapeutic management, we administered PD-L1, which successfully decreased the severity of EAN; it alleviated the neurologic course of EAN, as well as inhibited the infiltration of inflammatory cells and demyelination of sciatic nerves. Our data revealed that PD-L1 treatment inhibited lymphocyte proliferation and altered T cell differentiation by inducing decreases in IFN-γ+CD4+Th1 cells and IL-17+CD4+Th17 cells and increases in IL-4+CD4+Th2 cells and Foxp3+CD4+regulatory T cells. The expression levels of p-STAT3 and Foxp3 were significantly different in PD-L1-treated groups compared with the control group. Additionally, PD-L1 regulated the expression of Foxp3 and p-STAT3 in EAN, probably by inhibiting PI3K/AKT/mTOR signaling expression. In summary, PD-L1 is a potentially useful agent for the treatment of EAN because of its anti-inflammatory and neuroprotective effects.
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Yanan
authors: Y
authors: Ding
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Ranran
authors: R
authors: Han
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Wei
authors: W
authors: Jiang
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Jinting
authors: J
authors: Xiao
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Haijie
authors: H
authors: Liu
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Xiuju
authors: X
authors: Chen
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Xiaowen
authors: X
authors: Li
authors: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China hjw@tijmu.edu.cn.
authors: Junwei
authors: J
authors: Hao
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003711:Demyelinating Diseases / Q000517:prevention & control; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020275:Guillain-Barre Syndrome / Q000276:immunology; D007371:Interferon-gamma / Q000187:drug effects; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D017933:Peripheral Nervous System / Q000276:immunology*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells
chemical_list: D060890:B7-H1 Antigen; D020381:Interleukin-17; D015847:Interleukin-4; D007371:Interferon-gamma