Constitutive Neuronal Expression of the Immune Regulator, Programmed Death 1 (PD-1), Identified During Experimental Autoimmune Uveitis

Chen, Ling; Pai, Vicky; Levinson, Ralph D.; Sharpe, Arlene H.; Freeman, Gordon J.; Braun, Jonathan; Gordon, Lynn K.

doi:10.1080/09273940802491884

Cited by 39 publications

(28 citation statements)

References 27 publications

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“…34 In addition to altering the ratios of CD4 + T-cell subpopulations and correcting the inflammatory milieu, PD-L1 also showed the effects of changing BBB integrity and inhibiting cell loss after ICH. Because PD-1 has been reported to be constitutively expressed on neurons 7 and astrocytes, 9 it is conceivable that the interaction of PD-L1 with PD-1 expressed by neurons and astrocytes would lead to intensifying neuron and astrocyte loss in the PD-L1 group but ameliorate that status in the anti-PD-L1 mAb group, which is in contrast to our results. In the presence of PD-L1, there would be more neuron and astrocyte death because of PD-L1/PD-1 interactions but less cell damage from toxic factors like IL-1 and IL-6 released by proinflammatory Th1 and Th17 cells.…”

Section: Discussioncontrasting

confidence: 99%

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PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage–Induced Brain Injury

Han

Luo

Shi

et al. 2017

Stroke

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Background and Purpose— Intracerebral hemorrhage (ICH) is a neurologically destructive stroke, for which no valid treatment is available. This preclinical study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7 family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in a murine ICH model. Methods— ICH was induced by injecting autologous blood into 252 male C57BL/6 and Rag1 −/− mice. One hour later, ICH mice were randomly assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti–PD-L1 antibody. Neurological function was assessed along with brain edema, brain infiltration of immune cells, blood–brain barrier integrity, neuron death, and mTOR (mammalian target of rapamycin) pathway products. Results— PD-L1 significantly attenuated neurological deficits, reduced brain edema, and decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number of brain-infiltrating CD4 + T cells and the percentages of Th1 and Th17 cells but increased the percentages of Th2 and regulatory T cells. In the PD-L1–treated group, we observed an amelioration of the inflammatory milieu, decreased cell death, and enhanced blood–brain barrier integrity. PD-L1 also inhibited the mTOR pathway. The administration of anti–PD-L1 antibody produced the opposite effects to those of PD-L1 in ICH mice. Conclusions— PD-L1 provided protection from the damaging consequences of ICH.

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Section: Discussioncontrasting

confidence: 99%

“…6 Both PD-1 and B7-1 are reported to be expressed on neurons 7,8 and astrocytes. 9,10 B7-1 associates with PD-L1 with an affinity of about one third the affinity of PD-L1 for PD-1.…”

mentioning

confidence: 99%

PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage–Induced Brain Injury

Han

Luo

Shi

et al. 2017

Stroke

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“…Identification of PD-1 and it’s ligands in the retina and the establishment of their role in developmental RGC apoptosis has introduced a novel molecular mechanism for RGC death: that RGC apoptosis may be turned on by a negative signal delivered by receptor-ligand interaction through the PD-1 system (Chen et al, 2009a; Chen et al, 2009b; Sham et al, 2012). In this study we further demonstrate that PD-1 is dramatically upregulated in some RGCs after optic nerve injury, raising the possibility that PD-1 signaling pathway might be functionally important in pathological RGC cell loss in the adult animal.…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory previously reported that PD-1 is constitutively expressed in retina ganglion cells (RGCs), an unanticipated observation since PD-1 was previously believed to function exclusively within immune system (Chen et al, 2009a). Concordant with its functions in the immune system, we further demonstrated that PD-1 and its partner(s) play an important role in RGC death during retinal development (Chen et al, 2009b; Sham et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush

Wang

Chan

Qin

et al. 2015

Experimental Eye Research

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Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.

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“…It can also be expressed on non-lymphoid organs such as retina (Chen et al, 2009). PD-L1 has a wider range of expression including dendritic cells (Wolfle et al, 2011), macrophages (Wagner et al, 2010), neutrophils (Bankey et al, 2010) and activated T and B-lymphocytes (Francisco et al, 2010;Rosignoli et al, 2009).…”

Section: Expression Of Pd-1 and Its Ligandsmentioning

confidence: 99%

Co-Inhibitory Molecule Programmed Death-1 and Its Ligands: A New Alternative Therapy for Human Immunodeficiency Virus Infection?

Leon-Flores¹

2012

American Journal of Infectious Diseases

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Chronic viral infections are characterized by the up-regulation of a set of immunomodulatory receptors. The over-expression of co-inhibitory molecules on T cells leads to a dysfunctional T cell response with an "exhausted" phenotype. Programmed Death-1 (PD-1) is a molecule that exerts an inhibitory signal on the T cell receptor when it binds to the PD-L1 or PD-L2 ligands present on antigen-presenting cells. Also, the expression of these molecules has been associated to the loss of T cell functions as well as clinical markers of the progression of HIV infection. The study of these molecules has gained attention due to reports indicating that blockade of PD-1 pathway could partially reconstitute T cell functions. In fact, this mechanism has been proposed as an alternative treatment for some chronic viral infections such as HIV infection. This review is focused on those mechanisms that might be favouring the over-expression of PD-1 and its ligands during HIV infection and on the possible new approaches that, by reducing its expression, might represent new strategies for the treatment of HIV infection. Knowing the exact mechanism leading to PD-1, PD-L1 and PDL2 expression in physiologic and pathological conditions is essential for the development of successful treatments. Novel molecular mechanisms inhibiting PD-1 activation might have potential therapeutic use not only in HIV infection but also in other diseases.

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Constitutive Neuronal Expression of the Immune Regulator, Programmed Death 1 (PD-1), Identified During Experimental Autoimmune Uveitis

Cited by 39 publications

References 27 publications

PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage–Induced Brain Injury

PD-L1 (Programmed Death Ligand 1) Protects Against Experimental Intracerebral Hemorrhage–Induced Brain Injury

Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush

Co-Inhibitory Molecule Programmed Death-1 and Its Ligands: A New Alternative Therapy for Human Immunodeficiency Virus Infection?

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