Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Treg insufficiency in autoimmune diabetes is driven by selective loss of Neuropilin-1 on intra-islet regulatory T cells

ABSTRACT: Strategies targeting Treg insufficiency are vital for treating autoimmune diseases like T1D. Our findings highlight the critical role of Neuropilin 1 (Nrp1) in stabilizing Tregs within pancreatic islets. Boosting Nrp1 levels delays diabetes onset by enhancing Treg function. This underscores Nrp1 as a potential target for bolstering Treg activity and combating autoimmune diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE262874 | GEO | 2024/08/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Interferon-γ drives T reg fragility to promote anti-tumor immunity

Project description:Regulatory T cells (Tregs) are a barrier to effective anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune homeostasis, Treg-restricted Nrp1 deletion in mice results in profound tumor resistant due to Treg functional fragility. Drivers of Treg fragility, the mechanistic basis of Nrp1 dependency, and the relevance of these processes for human cancer and immunotherapy remain unknown. NRP1 expression on human Tregs in melanoma and HNSCC was highly heterogeneous and correlated with prognosis. Using a mouse model of melanoma in which mutant Nrp1-deficient (Nrp1–/–) and wild type (WT) Tregs could be assessed in a competitive environment, we found that a high proportion of intratumoral Nrp1–/– Tregs produce interferon-γ (IFNγ), which in turn drove the fragility of surrounding WT Tregs, boosting anti-tumor immunity and facilitating tumor clearance. We also show that IFNγ-induced Treg fragility is required for an effective response to PD1 immunotherapy, suggesting that cancer therapies promoting Treg fragility may be efficacious .

2017-05-22 | GSE97939 | GEO

Neuropilin-1 is Required for the Suppressive Function of Human Regulatory T Cells

Project description:Regulatory T cells (Tregs), lymphocytes that suppress immunological reactions, are of great interest for our comprehension of homeostasis and regulation in the immune system and as a therapeutic target in the treatment of both immune-mediated pathologies and reactivation of the immune response in patients with cancer. Understanding the molecular mechanisms by which these cells are regulated in respone to their environment will help to inform clinical strategies targeting Tregs. We hypothesised that Neuropilin-1, a transmembrane co-receptor for ligands of the semaphorin and growth factor families, promotes the suppressive function of human Tregs. Utilising in vitro lentivirus-mediated transduction with shRNA to knock down neuropilin-1 in primary human Tregs, we demonstrated that neuropilin-1 knockdown Tregs were severely impaired in their capacity to suppress cell proliferation in vitro and in their ability to prolong allograft survival in a humanised mouse model of transplantation. While neuropilin-1-KD Tregs exhibited no defects in survival, proliferation and activation upon stimulation in vitro, we hypothesised that loss of NRP1 expression would alter the global gene expression profile of human Tregs, revealing a NRP1-dependent Treg-associated transcriptional signature.

2019-01-01 | GSE106932 | GEO

RNAseq of HUVECs transfected with siRNA targeting Neuropilin 1 (NRP1) (si-NRP1) or a control non-targeting sequence (si-control) and exposed to unidirectional shear stress (20dyns/cm2), oscillatory flow (5dyn/cm2) or kept in absence of flow

Project description:HUVECs transfected with siRNA targeting Neuropilin 1(NRP1) (si-NRP1) or a control non-targeting sequence (si-control) and exposed to unidirectional shear stress (20dyns/cm2), oscillatory flow (5dyn/cm2) or kept in absence of flow.

2023-05-23 | E-MTAB-12191 | biostudies-arrayexpress

Neuropilin-1 high monocytes protect against neonatal inflammation

Project description:Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized with high levels of neuropilin-1 (Nrp1), termed Nrp1 high monocytes. Nrp1high monocytes displayed potent immunosuppressive activity as compared with their Nrp1low counterpart. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1 highmonocytes led to remission of NEC. Mechanistic studies showed that Nrp1, via binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These observations uncover an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for inflammatory disorders in neonates.

2024-04-12 | GSE263510 | GEO

Neuropilin 1 interactome in endothelial cells

Project description:To get unbiased insights on the molecular networks through by which Neuropilin 1 (NRP1) controls endothelial cell (EC) and blood vessel functions independently from its ligands, wehave implemented a Halo Tag (HT)-based approach, which enables effective surface labeling and pull-down of proteins, and combined it with quantitative mass spectrometry (MS) analysis.

2022-06-15 | PXD019700 | Pride

Neuropilin-1 mediates lung tissue-specific control of ILC2s function in type 2 immunity

Project description:ILC2s are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. But how they integrate to the respective tissue microenvironment to perform tissue-supportive functions remain poorly defined. Here, we identify neuropilin-1, which is induced postnatally and sustained by lung-derived TGFβ1, as a tissue signature of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses ILC2s function and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFβ1-Nrp1 signaling enhances ILC2s function and type 2 immunity through upregulation of IL-33 receptor ST2 expression. Our findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s activation and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis

2021-10-22 | GSE168809 | GEO

A proteomics approach to isolating neuropilin-dependent α5 integrin trafficking pathways: neuropilin 1 and 2 co-traffic α5 integrin through endosomal p120RasGAP to promote polarised fibronectin fibrillogenesis in endothelial cells

Project description:Integrin trafficking to and from membrane adhesions is a crucial mechanism that dictates many aspects of a cell’s behaviour, including motility, polarisation, and invasion. In endothelial cells (ECs), the intracellular traffic of α5-integrin is regulated by both neuropilin 1 (NRP1) and neuropilin 2 (NRP2), yet the redundancies in function between these co-receptors remain unclear. Moreover, the endocytic complexes that participate in NRP-directed-traffic remain poorly annotated. Here we identify an important role for the GTPase-activating protein p120RasGAP in ECs, promoting the recycling of α5-integrin from early endosomes. Mechanistically, p120RasGAP enables transit of endocytosed α5-integrin-NRP1-NRP2 complexes to Rab11+ recycling endosomes, promoting cell polarisation and fibronectin (FN) fibrillogenesis. Silencing of both NRP receptors, or p120RasGAP, resulted in the accumulation of α5-integrin in early endosomes, a loss of α5-integrin from surface adhesions, and attenuated EC polarisation. Endothelial-specific deletion of both NRP1 and NRP2 in the postnatal retina recapitulated our in vitro findings, severely impairing FN fibrillogenesis and polarised sprouting. Our data assign an essential role for p120RasGAP during integrin traffic in ECs and support a hypothesis that NRP receptors co-traffic internalised cargoes. Importantly, we utilise comparative proteomics analyses to, for the first time, isolate a comprehensive map of NRP1-dependent and NRP2-dependent-α5-integrin interactions in ECs.

2024-05-20 | PXD051778 | Pride

Potentiation of regulatory T cell stability and function via a neuropilin-1:semaphorin-4a axis

Project description:Regulatory T cells (Treg) represent a critical immunoregulatory component of the immune system. The signals that maintain Treg stability and potentiate their function remain obscure. Here we show that the immune cell surface ligand semaphorin-4a (Sema4a) Sema treated and NRP1 knock outs were compared to untreated wild type T cell controls

2013-09-06 | E-GEOD-41185 | biostudies-arrayexpress

The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling

Project description:Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion CBF::MYH11 oncoprotein regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBF::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBF::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy.

2024-11-18 | GSE215613 | GEO

Role of Neuropilin-1 in regulatory T cell stability and function

Project description:To investigate the function of Neuropilin-1 (NRP-1) in Foxp3+ regulatory T (Treg) cell stability and function, we cultured naïve CD4+ T cells under induced Treg cell (iTreg)-differentiating condition. We then flow sorted NRP-1+ and NRP-1- iTreg cells and performed gene expression profiling analysis.

2022-04-30 | GSE201416 | GEO

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