Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children

ABSTRACT: Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children

PROVIDER: PRJNA776144 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR16632354_1.fastq.gz	Fastqsanger.gz
	SRR16632354_2.fastq.gz	Fastqsanger.gz
	SRR16632355_1.fastq.gz	Fastqsanger.gz
	SRR16632355_2.fastq.gz	Fastqsanger.gz
	SRR16632356_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children

Project description:Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C additionally upregulated Notch1 expression. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variant impacting inflammation and autoimmunity pathways. Several variants mapped to Notch signaling-related genes including a loss of function mutation in the negative Notch1 regulator NUMB . Notch1 signaling in Treg cells induced CD22, leading to their destabilization in an mTORC1 dependent manner and to the promotion of systemic inflammation in proxy mouse models. These results establish the Notch1-CD22 axis as an immune dysregulatory mechanism critically involved in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

2021-12-01 | GSE186799 | GEO

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

Project description:Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.

2021-04-02 | GSE166489 | GEO

Plasma proteomics of Multisystem Inflammatory Syndrome in Children

Project description:Multisystem inflammatory syndrome in Children (MIS-C) occurs in children between two and six weeks following an initial SARS-CoV-2 infection. The mechanism through which a minority of children develop the hyperinflammation characteristic of MIS-C, while others remain well, is unknown. In this study we present an in-depth assessment of the proteome of children before and after SARS-CoV-2 infection, including children with MIS-C. Reassuringly, these data show that there were minimal changes to the circulating proteome in healthy children as result of SARS-CoV2 infection and there was no evidence of continued inflammation following SARS-CoV-2 infection in children. However, activation of pro-inflammatory pathways and raised circulating markers of myocardial and vascular damage were found to be significantly associated with MIS-C. Our findings have been verified in silico using publicly available proteomic datasets and hence several promising candidate biomarker proteins for diagnosis of MIS-C are identified and described herein.

2025-08-25 | PXD051939 | Pride

CD22 interactome

Project description:CD22 (Siglec-2) is a member of the Siglec family. It is an inhibitory co-receptor of the B-cell-receptor (BCR) and inhibits B–cell activation. Upon BCR stimulation ITIMs in the cytoplasmic tail of CD22 are phosphorylated. This triggers CD22 signalling pathways, which lead to a decreased calcium mobilization in the B cell and thus an inhibition of BCR signalling. Although some CD22 binding partners, such as the phosphatase SHP-1, have already been identified, we deciphered the CD22 interactome in more detail, to gain a deeper understanding of CD22 molecular mechanisms and signalling events after BCR activation. Stable isotope labelling of amino acids in cell culture (SILAC) in combination with mass spectrometry analysis enabled the identification of specific CD22 interaction partners in a quantitative proteomics approach. Hereby, several new CD22 associated proteins were identified that have not been linked to CD22 yet. One of those interacting proteins is cullin 3, an E3 ubiquitin ligase. It was revealed that cullin 3 is important for clathrin-dependent CD22 internalization after BCR stimulation and CD22 surface expression. Further analysis of B-cell specific cullin 3 deficient mice showed an important role of cullin 3 in B cell development. These mice have strongly reduced numbers of mature B cells in the periphery, which are characterized by increased CD22 expression and additionally by pre-activated and apoptotic phenotypes.

2020-05-06 | PXD013801 | Pride

The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Project description:Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcomes were previously correlated with Notch4 expression on Tregs, here, we show that Tregs in MIS-C were destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that patients with MIS-C had enrichment of rare deleterious variants affecting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Tregs induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results identify a Notch1/CD22 signaling axis that disrupts Treg function in MIS-C and point to distinct immune checkpoints controlled by individual Treg Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

| S-EPMC9797337 | biostudies-literature

CD22 modulation regulates neuroinflammation in microglia

Project description:Expression data comparing the effect of soluble CD22 in monocyte-derived microlgia and in mouse. Expression data on the effect of SM03 in Aβ-injected AD model in human CD22 transgenic mice.

2024-06-10 | GSE269121 | GEO

A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

Project description:A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

| PRJNA702761 | ENA

Transcriptional responses of T cells activated via CD22-specific T cell receptor compared to CD22-specific chimeric antigen receptor

Project description:Chimeric antigen receptor (CAR) T cells are effective against B-cell malignancies but are associated with cytokine-driven inflammatory toxicities such as cytokine release syndrome (CRS). Historically, T cell receptor (TCR) engineered T cell therapies are rarely associated with CRS. However, it is challenging to compare diverse cell products utilized in different clinical contexts and against different antigens. In this study, TCR and CAR were made to target the same source of antigen, CD22, expressed by B-cell malignancies: the TCR recognizes CD22-derived peptide processed and presented in the context of HLA-A*02:01, and the CAR recognizes CD22 protein expressed on the cell surface. In vivo studies comparing the CD22 TCR-T cells to CD22 CAR-T cells demonstrated that the TCR-T cells could clear leukemia without inducing systemic proinflammatory cytokine elevation, whereas CD22 CAR-T cells induced high levels of circulating proinflammatory cytokine reminiscent of CRS. T cells activated through either the TCR or CAR by an identical leukemia cell line demonstrated differential transcriptional responses. T cells activated via the CAR had disproportionate and significant upregulation of inflammatory gene sets compared to T-cells activated via the TCR.

2025-04-16 | GSE255323 | GEO

A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis [Bulk RNAseq]

Project description:SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of myocarditis, characterized by sustained NF-kB activity, associated with decreased gene expression of NF-kB inhibitors and TNF-a signaling . We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1a and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

2021-07-13 | GSE167028 | GEO

Identification of transcription factors regulating CD22 transcription

Project description:CD22 (also known as Siglec-2) belongs to the Siglec family of glycan-recognition proteins and negatively regulates B-cell receptor-mediated signaling. CD22 protein is known to be down-regulated in the B cells of patients with chronic lymphocytic leukemia (CLL). However, the mechanism regulating the transcription of CD22 is incompletely understood. In this study, we defined the minimal promoter region of the human CD22 gene, and systematically identified the proteins binding to the minimal promoter by DNA affinity-purification from the nuclear extracts of B cell lines and LC-MS/MS.

2025-03-26 | PXD054553 | 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