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PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE239875 | GEO | 2023/08/02

REPOSITORIES: GEO

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PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation.

Project description:Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS). Current therapies mainly target inflammatory processes during acute stages, but effective treatments for progressive MS are limited. In this context, astrocytes have gained increasing attention as they have the capacity to drive, but also suppress tissue-degeneration. Here we show that astrocytes upregulate the immunomodulatory checkpoint molecule PD-L1 during acute autoimmune CNS inflammation in response to aryl hydrocarbon receptor and interferon signaling. Using CRISPR-Cas9 genetic perturbation in combination with small-molecule and antibody-mediated inhibition of PD-L1 and PD-1 both in vivo and in vitro, we demonstrate that astrocytic PD-L1 and its interaction with microglial PD-1 is required for the attenuation of autoimmune CNS inflammation in acute and progressive stages in a mouse model of MS. Our findings suggest the glial PD-L1/PD-1 axis as a potential therapeutic target for both acute and progressive MS stages.

| S-EPMC10492803 | biostudies-literature

PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: IFNb]

Project description:Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS). Current therapies mainly target inflammatory processes during acute stages, but effective treatments for progressive MS are limited. In this context, astrocytes have gained increasing attention as they have the capacity to drive, but also suppress tissue-degeneration. Here we show that astrocytes upregulate the immunomodulatory checkpoint molecule PD-L1 during acute autoimmune CNS inflammation in response to aryl hydrocarbon receptor and interferon signaling. Using CRISPR-Cas9 genetic perturbation in combination with small-molecule and antibody-mediated inhibition of PD-L1 and PD-1 both in vivo and in vitro, we demonstrate that astrocytic PD-L1 and its interaction with microglial PD-1 is required for the attenuation of autoimmune CNS inflammation in acute and progressive stages in a mouse model of MS. Our findings suggest the glial PD-L1 / PD-1 axis as a new therapeutic target for both acute and progressive MS stages.

2023-08-02 | GSE239874 | GEO

PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: BMS202]

Project description:Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS). Current therapies mainly target inflammatory processes during acute stages, but effective treatments for progressive MS are limited. In this context, astrocytes have gained increasing attention as they have the capacity to drive, but also suppress tissue-degeneration. Here we show that astrocytes upregulate the immunomodulatory checkpoint molecule PD-L1 during acute autoimmune CNS inflammation in response to aryl hydrocarbon receptor and interferon signaling. Using CRISPR-Cas9 genetic perturbation in combination with small-molecule and antibody-mediated inhibition of PD-L1 and PD-1 both in vivo and in vitro, we demonstrate that astrocytic PD-L1 and its interaction with microglial PD-1 is required for the attenuation of autoimmune CNS inflammation in acute and progressive stages in a mouse model of MS. Our findings suggest the glial PD-L1 / PD-1 axis as a new therapeutic target for both acute and progressive MS stages.

2023-08-02 | GSE239873 | GEO

PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation

Project description:PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation

| PRJNA1001308 | ENA

PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: BMS202]

Project description:PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: BMS202]

| PRJNA1001312 | ENA

PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: IFNb]

Project description:PD-L1 positive astrocytes attenuate inflammatory functions of PD 1 positive microglia in models of autoimmune neuroinflammation [RNA-seq: IFNb]

| PRJNA1001314 | ENA

The immunomodulatory effect of microglia on ECM neuroinflammation via the PD-1/PD-L1 pathway.

Project description:IntroductionThe experimental cerebral malaria (ECM) model in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) has revealed microglia are involved in the ECM immune microenvironment. However, the regulation of microglia in the ECM immune response is not clear, and there is no safe and efficient treatment clinically for the protection of the nerve cells.AimsTo elucidate the negative regulation mechanism in the ECM brain mediated by microglia. Furthermore, to investigate protective effect of the appropriate enhancement of the PD-1/PD-L1 pathway in the brain against ECM through the intrathecal injection of the adenovirus expressing PDL1-IgG1Fc fusion protein.ResultsThe PD-1/PD-L1 pathway was induced in the ECM brain and showed an upregulation in the microglia. Deep single-cell analysis of immune niches in the ECM brainstem indicated that the microglia showed obvious heterogeneity and activation characteristics. Intrathecal injection of recombinant adenovirus expressing PD-L1 repressed the neuroinflammation and alleviated ECM symptoms. In addition, the synergistic effect of artemisinin and intracranial immunosuppression mediated by PD-L1 was more efficacious than either treatment alone.ConclusionThe appropriate enhancement of the PD-1/PD-L1 pathway in the early stage of ECM has an obvious protective effect on the maintenance of immune microenvironment homeostasis in the brain. Regulating microglia and the PD-1/PD-L1 pathway could be considered as a promising approach for protection against human cerebral malaria in the future.

| S-EPMC8673706 | biostudies-literature

Microglial PD-1 modulates neuroinflammation and Alzheimer's disease pathology by astrocytic PD-L1

Project description:Neuroinflammation, a pathogenic component of Alzheimer disease (AD), may limit the ability of the brain to clear deposits and debris. Tight control of the immune system may therefore be key to sustain the ability of the brain for repair and clearance. Here we report that PD-L1 on astrocytes and its receptor PD-1 on microglia, known for its inhibitory immune function, are upregulated around amyloid plaques in AD and APP/PS1 mice. Juxtamembrane shedding of PD-L1 was observed from astrocytes suggesting ectodomain signaling to microglial PD-1. Deletion of PD-1 in microglia evoked an inflammatory response and compromised Aβ uptake. Likewise, in APP/PS1 PD-1-/- mice increased deposition of amyloid β (Aβ), reduced microglial Aβ uptake, and decreased expression of the Aβ receptor CD36 on microglia were detected. Therefore, ineffective immune regulation by the PD-1/PD-L1 axis contributes to Aβ plaque deposition during chronic, unresolved neuroinflammation in AD.

| S-SCDT-EMBOJ-2021-108662 | biostudies-other

Expression data in PD-L1 positive and PD-L1 negative human melanoma samples

Project description:Blocking the PD-1/PD-L1 immunosuppressive pathway has shown promise in the treatment of certain cancers including melanoma. This study investigates differences in the gene expression profiles of human melanomas that do or do not display the immunosuppressive protein PD-L1. Further understanding of genes expressed within the tumor microenvironment of PD-L1+ tumors may lead to improved rationally designed treatments. Gene expression profiling was performed on total RNA extracted by laser capture microdissection from 11 archived formalin-fixed paraffin-embedded (FFPE) melanoma specimens, 5 of which were PD-L1 positive and 6 PD-L1 negative. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: Janis M. Taube, Geoffrey D. Young, Tracee L. McMiller, Shuming Chen, January T. Salas, Theresa S. Pritchard, Haiying Xu, Alan K. Meeker, Jinshui Fan, Chris Cheadle, Alan E. Berger, Drew M. Pardoll, and Suzanne L. Topalian, Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade, Clin Cancer Res 2015, in press.

2015-05-01 | E-GEOD-65041 | biostudies-arrayexpress

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

Project description:Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia.The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta42 (A?42) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain.Quantitative results revealed that GLP down-regulates LPS- or A?-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions.Overall, our study provides an insight into the GLP regulation of LPS- and A?-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

| S-EPMC5364682 | biostudies-other

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