Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ScRNA-seq of immune cells in tumors or during EAE from Pglyrp1 KO and wildtype mice.

ABSTRACT: PGLYRP1 is highly co-expressed with known co-inhibitory molecules and might be a promising novel target for immunotherapy. Indeed, genetic deletion of PGLYRP1 in mice led to decreased tumor growth and an increased activation/effector phenotype in CD8+ T cells, suggesting an inhibitory function of PGLYRP1 in CD8+ T cells. Surprisingly, genetic deletion of PGLYRP1 strongly protected against experimental autoimmune encephalomyelitis (EAE), a model of autoimmune disease in the central nervous system (CNS). Pglyrp1-deficient myeloid cells had a defect in antigen-presentation and T cell activation, indicating that PGLYRP1 might act as a proinflammatory molecule in myeloid cells during autoimmunity. Our results highlight PGLYRP1 as a promising novel target for immunotherapy, that, when targeted, elicits a potent anti-tumor immune response while protecting against tissue inflammation and autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE223873 | GEO | 2023/06/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Bulk RNA-seq of Pglyrp1 KO Tumor Infiltrating CD8+ T cells

Project description:To characterize the role of Pglyrp1 in tumor immunity, we performed bulk RNA-seq for MC38-OVA tumor infiltrating CD8+ T cells from wild type and Pglyrp1-deficient mice.

2023-06-12 | GSE223872 | GEO

Gene expression in the colon of DSS-treated Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice

Project description:Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice are all more sensitive than wild type (WT) mice to dextran sulfate sodium (DSS)-induced colitis. The purpose of this study was to determine which genes are differentially induced by DSS treatment in the colon of Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice compared to WT mice. The results demonstrate higher induction of proinflammatory gene expression in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice than in WT mice after DSS treatment. The majority of genes whose expression is increased in Pglyrp1-/-, Pglyrp2-/-, Pglyrp3-/-, and Pglyrp4-/- mice but not in WT mice are interferon-inducible genes. Thus, Peptidoglycan Recognition Proteins Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4 protect mice from excessive inflammatory response and damage to the colon by limiting expression of interferon-inducible genes in the colon.

2010-08-23 | GSE18859 | GEO

Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3

Project description:CD8+ T cell exhaustion is a distinct differentation state resulting from chronic antigen exposure and leading to hierarchical loss of effector functions. Using a murine model of diabetes, we show that CD8+ T cells derived from the islets of diabetic mice have CD8+ T cells that are canonically exhausted and yet retain sufficient effector function to contribute to pathogenicity in autoimmune diabetes. Genetic deletion of the inhibitory receptor LAG3 restricted to only CD8+ T cells lead to accelerated disease, with LAG3 deficient CD8+ T cells having enhanced effector function and trafficking. These findings reveal a distinct role of LAG3 in restraining autoreactive CD8+ T cells and implicate LAG3 as a potential therapeutic target in autoimmunity.

2022-04-08 | GSE199357 | GEO

RNA-Seq of IL-2-KO follicular CD8 T cells and IL-2-KO follicular CD4 T cells

Project description:Follicular CXCR5+ PD-1+ CD8 T cells (CD8 Tfc) arise in multiple models of systemic autoimmunity yet their functional contribution to disease remains in debate. Here we define the follicular localization and functional interactions of CD8 Tfc with B cells during autoimmune disease. The absence of functional T regulatory cells in autoimmunity allows for CD8 Tfc development that then expands with lymphoproliferation. CD8 Tfc are identifiable within the lymph nodes and spleen during systemic autoimmunity, but not during tissue-restricted autoimmune disease. Autoimmune CD8 Tfc cells are polyfunctional, producing helper cytokines IL-21, IL-4, and IFNγ while maintaining cytolytic proteins CD107a, granzyme B, and TNF. During autoimmune disease, IL-2-KO CD8 T cells infiltrate the B cell follicle and germinal center, including the dark zone, to induce AID in vitro in naïve B cells via IL-4 secretion. CD8 Tfc represent a unique CD8 T cell population with a diverse effector cytokine repertoire that can contribute to pathogenic autoimmune B cell response.

2022-01-22 | GSE177911 | GEO

Transcriptional profiling of human KIR+ and KIR- CD8 T cells by bulk RNA-seq

Project description:Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalents of the Ly49 family, in the blood and inflamed tissues of various human autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients’ leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and correlate with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.

2022-03-08 | GSE168527 | GEO

Inhibition of p300 impairs Foxp3+ T-regulatory cell function and promotes anti-tumor immunity

Project description:Foxp3+ T-regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity, but can also curtail host responses to cancers. Tregs are therefore promising targets to enhance anti-tumor immunity. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and non-histone proteins. We found that conditional deletion or pharmacologic inhibition of one specific HAT, p300, in Foxp3+ Tregs, increased TCR-induced apoptosis in Tregs, impaired Treg suppressive function and iTreg peripheral conversion, and limited tumor growth in immunocompetent, but not in immunodeficient, hosts. Our data demonstrate that p300 is important for Foxp3+ Treg function and homeostasis in vivo and in vitro, and identify a novel mechanism to diminish Treg function without overtly impairing effector Tcell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice, compared to wild type (Foxp3cre) control (all C57Bl/6 background).

2013-08-18 | E-GEOD-47989 | biostudies-arrayexpress

Real-time quantitative PCR analysis of mRNA from lungs of WT and Pglyrp1-/- mice sensitized with HDM

Project description:Wild type (WT) and Pglyrp1-/- mice were treated with PBS or sensitized 5 days/week for 3 or 5 weeks with 10 M-BM-5l per application of 2.5 mg/ml of purified house dust mite allergen. 3 days after the last sensitization the lungs were removed and homogenized, and RNA was isolated from the right lobes using the TRIZOL method. Quantitative reverse transcription real-time PCR (qRT-PCR) was used to quantify the amounts of mRNA in the lungs using custom RT2 Profiler PCR Arrays designed by us and manufactured by Qiagen/SA Biosciences. qRT-PCR gene expression profiling

2012-12-25 | E-GEOD-43137 | biostudies-arrayexpress

AIM2 in regulatory T (Treg) cells restrains autoimmune diseases

Project description:The inflammasome initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells1,2. It is comprised of an innate immune receptor/effector, pro-caspase-1 and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD). Consistent with their pro-inflammatory function, inflammasome components including caspase-1, ASC and NLRP3, are known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1 and IL-18 secretion in myeloid cells3-6. Here we show an unexpected function of a DNA-binding inflammasome effector, AIM2 (Absent in Melanoma 2)7-10, in restraining autoimmunity by performing EAE in both whole body and Treg-specific deletion of Aim2–/– mice. AIM2 is highly expressed by human and mouse Treg cells and it is essential to attenuate EAE. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates mTOR, Myc and immune-metabolic functions in both Treg cells isolated in vivo and Treg cells induced in vitro with TGF-. Importantly, we found AIM2 physically interacted with RACK1 in Treg cells to facility the PP2A/RACK1/Akt-mTOR signaling, which is identified as a central component downstream of AIM2 that controls Treg cell function and stability. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report reveals a previously unappreciated T cell-intrinsic role of AIM2 in maintaining Treg cell function to restrain autoimmunity. This is achieved by diminishing Akt-mTOR signaling to regulate Treg stability under inflammation, and altering immune-metabolism in Treg cells.

2021-01-27 | PXD018638 | Pride

Transcription profiling of human CD8 T cells in systemic lupus erythematosus (SLE) and vasculitis

Project description:Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Clinically useful biomarkers have been identified using DNA microarrays in cancer but not autoimmunity. We show that transcriptional profiling of purified CD8 T cells, but not unseparated cells, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV) and systemic lupus erythematosus (SLE). We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8 T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest novel potential therapeutic targets in autoimmunity.

2010-06-02 | E-MTAB-157 | biostudies-arrayexpress

Interconnected lineage trajectories link conventional and NK-like exhausted CD8+ T cells beneficial in T1D [P362-1]

Project description:While distinct NK-like CD57+ and PD-1+ CD8+ exhausted T cell populations (Tex) were both linked to beneficial immunotherapy response in autoimmune Type 1 Diabetes (T1D) patients, relationships between these cell types are poorly understood. We show that PD-1+ and CD57+ Tex populations in this context were epigenetically similar, but CD57+ Tex cells displayed unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1+ and CD57+ Tex also showed reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57+ Tex showed unappreciated gene expression heterogeneity and shared clonal relationships with PD-1+ Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1+, Tex-CD57+, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.

2024-01-17 | GSE237611 | 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