Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

ABSTRACT: Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

PROVIDER: PRJNA861288 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR20439800_1.fastq.gz	Fastqsanger.gz
	SRR20439800_2.fastq.gz	Fastqsanger.gz
	SRR20439801_1.fastq.gz	Fastqsanger.gz
	SRR20439801_2.fastq.gz	Fastqsanger.gz
	SRR20439802_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 44

Similar Datasets

Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

Project description:Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

| PRJNA860545 | ENA

Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

Project description:Checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 and CTLA-4 have revolutionized cancer treatment but can trigger autoimmune complications including CPI-induced diabetes (CPI-DM), which occurs preferentially with PD-1 blockade. We found evidence of pancreatic inflammation in patients with CPI-DM with shrinkage of pancreases, increased pancreatic enzymes, and in a case from a patient who died with CPI-DM, peri-islet lymphocytic infiltration. In the NOD mouse model, anti-PD-L1 but not anti-CTLA-4 induces DM rapidly. RNA sequencing revealed that cytolytic IFNγ+ CD8+ T cells infiltrated islets with anti-PD-L1. Changes in β cells were predominantly driven by IFNγ and TNFα and included induction of a novel β cell population with transcriptional changes suggesting dedifferentiation. IFNγ increased checkpoint ligand expression and activated apoptosis pathways in human β cells in vitro. Treatment with anti-IFNγ and anti-TNFα prevented CPI-DM in anti-PD-L1 treated NOD mice. CPIs targeting the PD-1/PD-L1 pathway result in transcriptional changes in β cells and immune infiltrates that may lead to the development of diabetes. Inhibition of inflammatory cytokines can prevent CPI-DM, suggesting a strategy for clinical application to prevent this complication.

2022-10-27 | GSE209587 | GEO

Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes

2022-10-27 | GSE208644 | GEO

Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor-induced diabetes.

Project description:Checkpoint inhibitors (CPIs) targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have revolutionized cancer treatment but can trigger autoimmune complications, including CPI-induced diabetes mellitus (CPI-DM), which occurs preferentially with PD-1 blockade. We found evidence of pancreatic inflammation in patients with CPI-DM with shrinkage of pancreases, increased pancreatic enzymes, and in a case from a patient who died with CPI-DM, peri-islet lymphocytic infiltration. In the NOD mouse model, anti-PD-L1 but not anti-CTLA-4 induced diabetes rapidly. RNA sequencing revealed that cytolytic IFN-γ+CD8+ T cells infiltrated islets with anti-PD-L1. Changes in β cells were predominantly driven by IFN-γ and TNF-α and included induction of a potentially novel β cell population with transcriptional changes suggesting dedifferentiation. IFN-γ increased checkpoint ligand expression and activated apoptosis pathways in human β cells in vitro. Treatment with anti-IFN-γ and anti-TNF-α prevented CPI-DM in anti-PD-L1-treated NOD mice. CPIs targeting the PD-1/PD-L1 pathway resulted in transcriptional changes in β cells and immune infiltrates that may lead to the development of diabetes. Inhibition of inflammatory cytokines can prevent CPI-DM, suggesting a strategy for clinical application to prevent this complication.

| S-EPMC9536276 | biostudies-literature

Cytocidal Macrophages Cause Acute Diabetes following Checkpoint Blockade of PD-1 in NOD Mice

Project description:Cytocidal Macrophages Cause Acute Diabetes following Checkpoint Blockade of PD-1 in NOD Mice

| PRJNA631406 | ENA

Interleukin 21 drives CXCR6+ CD8+ T cell mediators in Autoimmune Checkpoint Inhibitor Thyroiditis

Project description:Interleukin 21 drives CXCR6+ CD8+ T cell mediators in Autoimmune Checkpoint Inhibitor Thyroiditis

| PRJNA905392 | ENA

Field conditions modify ACD6

Project description:Field conditions modify ACD6

| PRJEB78910 | ENA

Cytocidal Macrophages Cause Acute Diabetes following Checkpoint Blockade of PD-1 in NOD Mice

Project description:Blocking the action of the PD-1 protein in lymphocytes results in their activation leading to an effective immune response in cancers and in experimental viral infections. But such immunotherapy in clinical cases results in immune adverse effects among them the development of autoimmune diabetes. In the diabetes susceptible NOD mice, blockade of the PD-L1/PD-1 pathway during the pre-diabetic stage results in severe and acute diabetes. Single-cell RNA sequencing and flow cytometry analysis of islets following blockade of the PD-L1/PD-1 pathway identified a cascade of cellular interactions involving resident macrophages and diabetogenic T cells. Such reactions led to the recruitment of monocyte derived macrophages that caused diabetes. Elimination of the monocyte derived macrophages resulted in protection. The cytocidal activity was highly dependent on IFNγ signaling and the downstream release of nitric oxide by the monocyte derived macrophages. The activation of macrophages required both the participation of CD4 and CD8 T cells. Our studies call attention to macrophages as the major effector cell following blockade of PD-1. Targeting the monocyte-derived macrophage provides a new option to prevent and treat immune checkpoint blockade induced diabetes and perhaps other immune adverse reactions.

2020-11-12 | GSE150178 | GEO

DNA damage checkpoint kinases regulate a global network of transcription factors

Project description:DNA damage results in the activation of checkpoint kinases, which phosphorylate downstream effectors that inhibit the cell cycle, activate DNA repair, and cause widespread changes in transcription. However, the specific connections between the checkpoint kinases and downstream transcription factors (TFs) are not well understood. Here, we introduce a strategy for mapping regulatory networks between kinases and TFs involving integration of kinase mutant expression profiles, transcriptional regulatory interactions, and phosphoproteomics. We use this approach to investigate the role of the Saccharomyces cerevisiae checkpoint kinases (Mec1, Tel1, Chk1, Rad53, and Dun1) in the transcriptional response to DNA damage caused by methyl methanesulfonate (MMS). The result is a global kinase-TF regulatory network in which Mec1 and Tel1 signal through Rad53 to synergistically regulate the expression of more than 600 genes. This network implicates at least nine TFs, including Msn4, Gcn4, SBF (Swi4/Swi6), MBF (Swi6/Mbp1), and Fkh2/Ndd1/Mcm1, nearly all of which have sites of Rad53-dependent phosphorylation, as downstream regulators of checkpoint kinase-dependent genes. We also identify a major DNA damage-induced transcriptional network acting independently of Rad53 and other checkpoint kinases to regulate expression of genes involved in general and oxidative stress responses. Expression was profiled with and without MMS treatment in several genetic backgrounds (gene deletion strains).

2013-03-31 | E-GEOD-40351 | biostudies-arrayexpress

Type 1 Diabetes DNA Damage Checkpoint Pathway Quantitation

Project description:iTRAQ-based quantitative proteomics and phosphoproteomics analyses of induced pluripotent stem cells (iPSC) from patients with longstanding type 1 diabetes. "Preserved DNA Damage Checkpoint Pathway Protects From Complications in Long-standing Type 1 Diabetes", Cell Metabolism, in press.

2015-07-08 | MSV000079185 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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