Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (EV-treated)

ABSTRACT: Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE242564 | GEO | 2024/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (PD in vivo)

Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.

2024-05-24 | GSE242563 | GEO

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (tRF overexpression)

2024-05-24 | GSE242561 | GEO

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (NOD islets)

2024-05-24 | GSE242567 | GEO

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (Cyt-treated)

2024-05-24 | GSE242566 | GEO

Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (NOD EVs)

2024-05-24 | GSE242565 | GEO

Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

Project description:Type 1 and type 2 diabetes (T1D and T2D) share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, while beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alter the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role for beta cell fragility in genetic predisposition to diabetes.

2016-02-24 | PXD000859 | Pride

Genome-Wide Gene Expression Profiles in the Pancreatic Lymph Nodes of non-obese diabetic (NOD) mice

Project description:Type 1 diabetes (T1D) is a polygenic autoimmune disorder caused by autoreactive T cells that recognize pancreatic islet antigens and subsequently destroy insulin-producing β-cells. Pancreatic lymph nodes (PLN) are an essential site for the development of T1D, where tolerance to pancreatic self-antigens is first broken and the autoimmune responses are amplified. The purpose of this study was to identify candidate genes and pathways in the PLN that may contribute to the pathogenesis of T1D using a mouse model of T1D. Genome-wide gene expression was measured in individual NOD PLN at 10 days (n=6), 4 weeks (n=6) or 12 weeks of age (n=5), against a pooled sample of age-matched NOD.B10 PLN as the control (n≥6), using Agilent Whole Mouse Genome Microarrays.

2015-03-09 | E-GEOD-66658 | biostudies-arrayexpress

Proteomics of Enriched Insulin Secretory Granules Fractionated by Size Exclusion Chromotography

Project description:Hybrid insulin peptides (HIPs) form in pancreatic beta-cells through the formation of peptide bonds between proinsulin fragments and other peptides. HIPs, which have been confidently identified in pancreatic islets by mass spectrometry, are targeted by CD4 T cells in subjects with Type 1 Diabetes (T1D), as well as by disease-triggering CD4 T cell clones in non-obese diabetic (NOD) mice. The mechanism(s) of HIP formation are currently poorly understood; however, it is well established that proteases can drive the formation of new peptide bonds in a side reaction during peptide bond hydrolysis. Here, we used a proteomic strategy on enriched insulin granules and identified cathepsin D (CatD) as the primary protease driving the specific formation of HIPs that are targeted by disease-relevant CD4 T cells in T1D. We also established that NOD islets deficient of cathepsin L (CatL), another protease that was implied in the formation of disease-relevant HIPs, contain elevated levels of HIPs, signifying a primary role for CatL in the proteolytic degradation of HIPs. In summary, our data suggest that CatD may be a therapeutic target in efforts to prevent or slow down the autoimmune destruction of beta-cells mediated by HIP-reactive CD4 T cells in T1D.

2023-11-16 | PXD032664 | Pride

Increased β-cell proliferation prior to immune-cell invasion prevents progression of type 1 diabetes

Project description:Type 1 diabetes (T1D) is characterized by pancreatic islet infiltration by autoreactive immune cells and a near-total loss of β-cells. Restoration of insulin-producing β-cells coupled with immunomodulation to suppress the autoimmune attack has emerged as a potential approach to counter T1D. Here we report that enhancing β-cell mass in female NOD mice early in life (prior to weaning) results in immunomodulation of T-cells, reduced islet infiltration and lower β-cell apoptosis, that together protect them from developing T1D. We observed that a model exhibiting β-cell hyperplasia on the NOD background (NOD-LIRKO) displayed altered β-cell antigens, and islet transplantation studies showed prolonged graft survival of NOD-LIRKO islets even upon exposure to diabetogenic splenocytes in vivo. Adoptive transfer of splenocytes from the NOD-LIRKOs prevented diabetes development in pre-diabetic NOD mice, while conversely, similar protective outcomes were obtained when NOD-LIRKO splenocytes were adoptively transferred after mixing them with diabetogenic NOD splenocytes in a dose-dependent manner. A significant increase in the splenic CD4+CD25+FoxP3+ regulatory T-cell (Treg) population in the NOD-LIRKO mice was observed to drive the protected phenotype since Treg depletion rendered NOD-LIRKO mice diabetic. The increase in Tregs coupled with a downregulation of key mediators of cellular function, upregulation of apoptosis and activation of TGF-β/SMAD3 signaling pathway in pathogenic T-cells favored reduced ability to kill β-cells. These data provide novel evidence that initiating β-cell proliferation, alone, prior to islet infiltration by immune cells alters the identity of β-cells, decreases pathologic self-reactivity of effector cells and increases Tregs to prevent progression of T1D.

2019-03-29 | GSE128315 | GEO

NOD Mouse Islet Peptide Content Identification

Project description:Beta-cells produce hybrid insulin peptides (HIPs) by linking insulin fragments to other peptides through peptide bonds. HIPs have unique amino acid sequences and are targeted by autoreactive T cells in type 1 diabetes (T1D). Individuals with recent-onset T1D have significantly higher levels of HIP-reactive T cells in their blood compared to non-diabetic control subjects. HIP-reactive T cells have also been found in the residual pancreatic islets of deceased T1D organ donors. In non-obese diabetic (NOD) mice, a major T1D animal model, several CD4 T cell clones that trigger diabetes have been shown to target HIPs. Through mass spectrometry, a subgroup of HIPs containing N-terminal amine groups of various peptides linked to aspartic acid residues of insulin C-peptide has been detected in NOD islets. Our research reveals that these HIPs form spontaneously in beta-cells via an aspartic anhydride intermediate mechanism. This process leads to the creation of a regular HIP with a standard peptide bond and a HIP-isomer (isoHIP) with an isopeptide bond linked to the carboxylic acid side-chain of the aspartic acid residue. Our mass spectrometric analyses confirmed the presence of both HIP isomers in murine islets, thereby validating the occurrence of this new reaction mechanism in beta-cells. The spontaneous formation of neoepitopes through the development of new peptide bonds within cells may contribute to the pathogenesis of T1D and other autoimmune diseases.

2023-11-16 | PXD041616 | Pride

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