Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protein Kinase C Delta Regulates Mononuclear Phagocytes by Repressing Type I and II Interferon Signaling and Hinders Response to Immunotherapy in Cancer

ABSTRACT: Mononuclear phagocytes (MPs) comprise monocytes, macrophages and dendritic cells and play a crucial role in tissue homeostasis. However, accumulating evidence suggests that mononuclear phagocytes contribute to tumor progression and resistance to checkpoint blockade. Protein kinase C delta (PKCδ) is a serine/threonine kinase that plays a crucial role in regulating the immune response by preventing autoimmunity. However, the role of PKCδ in antitumor immunity is unknown. In this study, we found that PKCδ is abundantly expressed by MPs in several human and mouse tumors. PKCδ-/- mice were more resistant to growth of various cancers compared to wild-type mice and were more responsive to anti-PD-1 immunotherapy. Furthermore, we found that tumors from PKCδ-/- mice harbor a Th-1-skewed immune response including increased antigen cross-presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in wild-type mice, but not in PKCδ-/- mice. In addition, co-injection of PKCδ-/- M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to wild-type M2-like macrophages co-injected with cancer cells. Finally, intrinsic loss of PKCδ functionally reprogrammed macrophages and dendritic cells by promoting their antigen presenting and cross-presenting capacity and triggered Type I and II interferon signaling. Our results suggest that PKCδ can be targeted to reprogram mononuclear phagocytes and augment checkpoint blockade efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE208394 | GEO | 2022/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Identification of Fcmr-dependent heterogeneity in tumor associated mononuclear phagocytes

Project description:The mononuclear phagocytic system (MPS) is characterized by functional diversity and plasticity, including within the tumor microenvironment (TME). Tumor-associated mononuclear phagocytes (TMPs) within the TME come from various ontological origins. To determine how Fcmr deficiency might impact the functional heterogeneity of mature mononuclear phagocytes (MPs) within the TME, we performed single-cell RNA sequencing (scRNAseq) on MPs isolated from B16 tumors resected from Fcmr-/- and Fcmr+/+ mice. To evaluate a homogenous population of MPs within the TME we chose to examine cells harboring expression of markers found in more mature, differentiated MPs. Therefore, we then sorted MerTk+ CD64+ TMPs by FACS and subjected these cells to single-cell transcriptomic analyses using the Chromium 10X Genomics platform. We obtained RNAseq profiles from 6352 Fcmr+/+ and 7999 Fcmr-/- TMPs.

2019-06-18 | GSE130287 | GEO

Total blood monocyte gene expression from neovascular age-related macular degeneration patients and age-matched controls

Project description:Mononuclear phagocytes (MPs), including monocytes and macrophages, play complex roles in the pathogenesis of age-related macular degeneration (AMD). We aimed to perform global transcriptome analysis on monocytes from AMD patients to obtain additional insight to the role of MPs in AMD. Peripheral blood was taken from treatment-naïve neovascular AMD (nvAMD) patients (n=14), and age-matched controls (n=15). Peripheral blood mononuclear cells (PBMCs) were separated and monocytes were isolated via negative selection. Gene expression was evaluated with Affymetrix Gene1.0 ST microarrays. Statistical/bioinformatics analysis was performed using open sourceware programs.

2017-02-10 | GSE76237 | GEO

CX3CR1+ mononuclear phagocytes gene-expression profile based on their location in the epididymis using RNA-sequencing

Project description:In the epididymis, prevention of autoimmune responses against spermatozoa, while providing protection against pathogens, is important for male fertility. We previously showed that immune cells known as mononuclear phagocytes (MPs) are located either in the epididymal interstitium or in close proximity to the epithelium. In the initial segments (IS), these “intraepithelial” MPs extend slender luminal-reaching projections between epithelial cells. In this study, we performed an in-depth characterization of MPs isolated from IS, caput-corpus, and cauda epididymis of CX3CR1EGFP+/- mice that express EGFP in these cells. Flow cytometry analysis revealed region-specific subsets of MPs that express combinations of markers traditionally described in ‘dendritic cells’ or ‘macrophages’. RNA sequencing identified distinct transcriptomic signatures in MPs from each region, and revealed specific genes involved in inflammatory and anti-inflammatory responses, phagosomal activity, and antigen processing and presentation. Functional fluorescent in vivo labeling assays showed that higher percentages of CX3CR1+ MPs that captured and processed antigens were detected in the IS compared to other regions. Confocal microscopy showed that in the IS and corpus, circulatory antigens were internalized and processed by interstitial and intraepithelial MPs. However, in the cauda only interstitial MPs internalized and processed antigens, while intraepithelial MPs did not take up antigens, indicating that all antigens have been captured before they reached the epithelial lining. Cauda MPs may thus confer a stronger protection against blood-born pathogens compared to proximal regions. By identifying immunoregulatory mechanisms in the epididymis, our study may lead to new therapies for common disorders such as male infertility and epididymitis, and identify potential targets for immuno-contraception.

2020-02-29 | GSE136442 | GEO

Gene expression in alveolar macrophages between bleomycin–treated wild-type and S1pr2-/- mice.

Project description:We compared mRNA expression in alveolar macrophages between bleomycin–treated wild-type and S1pr2-/- mice, using DNA microarray analysis. In S1pr2-/- macrophages, 398 genes showed decreases to less than 50% of the levels in wild-type macrophages. In contrast, 122 genes showed more than 2.0-fold increases in S1pr2-/- macrophages compared with wild-type macrophages. The downregulated genes in S1pr2-/- mice included the following potentially fibrosis–related genes: profibrotic cytokines, chemokines, and the markers characteristic of classically activated (M1) and alternatively activated (M2) macrophages.

2018-05-30 | GSE85411 | GEO

Mononuclear phagocytes in muscle after notexin injury in C57Bl/6, Cx3cr1-/-, Ccl2-/-,Cx3cr1-/-Ccl2-/- mice

Project description:Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2-/- mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is up-regulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2-/- mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration.

2015-09-29 | GSE73473 | GEO

MS-based proteomic characterization of Toxoplasma gondii GRA28-associated complexes

Project description:The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for systemic dissemination. We report that, upon T. gondii infection, macrophages initiate expression of transcription factors normally attributed to DCs, upregulate the expression of Ccr7 with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We identify the parasite effector GRA28, which is secreted into the host cell nuclei, as driving the chemotactic migratory activation of parasitized macrophages. To gain insight about the molecular role played by GRA28 in this phenomenon, we characterized its interactome.

2022-11-02 | PXD032360 | Pride

Existence of conventional dendritic cells in Gallus gallus revealed by comparative gene expression profiling

Project description:The existence of conventional dendritic cells (cDCs) has not yet been demonstrated outside mammals. In this paper, we identified bona fide cDCs in chicken spleen. Comparative profiling of global and of immune response gene expression, morphology, and T cell activation properties show that cDCs and macrophages (MPs) exist as distinct mononuclear phagocytes in chicken, resembling their human and mouse cell counterparts. Using computational analysis, core gene expression signatures for cDCs, MPs, T and B cells across chicken, human and mouse were established, which will facilitate the identification of these subsets in other vertebrates. Overall this study, by extending the newly uncovered cDC and MP paradigm to chicken, suggests that the generation of these two phagocyte lineages occurred before the reptile to mammal and bird transition in evolution. It opens avenues for the design of new vaccines and neutraceuticals that are mandatory for the sustained supply of poultry products in the expanding human population. Four independent replicates of RNA from 4 cellular populations have been purified from histocompatible chicken spleens, based on surface markers and fluorecence cell sorting: putative conventional Dendritic cells (F2+, MHC-II+ cells) ; control B cells (BU-1+ cells; only 3 replicates could be included in the study); T cells (CD3+ cells) and macrophage spleen population (MHC-II+, KUL-01+ cells).

2014-05-01 | E-GEOD-55642 | biostudies-arrayexpress

Single-cell transcriptome sequencing of macrophages in acute kidney injury

Project description:We uesd single-cell transcriptome sequencing technology to sequence the mononuclear phagocytes in the mice kidney, blood and spleen after acute kidney injury, and comprehensively describe characteristics of mononuclear phagocytes.

2022-02-09 | GSE174324 | GEO

Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes

Project description:Transcriptome analysis of two population of peritoneal mononuclear phagocytes (CD14+ macrophages and CD1c+ dendritic cells) in peritoneal dialysis effluent from stable (infection-free) peritoneal dialysis patients.

2017-01-23 | E-MTAB-5439 | biostudies-arrayexpress

Effect of depletion of OGT on gene expression during M2 polarization of macrophages

Project description:To investigate the function OGT in the regulation of M2 polarization of macrophages, we established IL-4-activated bone marrow-derived macrophages (BMDMs) from mice of wild-type control or Lyz2-Cre/Loxp-mediated knockout of OGT. We then performed gene expression profiling analysis using data obtained from RNA-seq of wild-type (WT) and OGT-knockout (OGT-KO) macrophages at two time points during IL-4 (20ng/μl) sitmulation.

2022-09-08 | GSE210176 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data