Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SKI is critical to counter TGF-β signaling to promote T cell function and autoimmunity

ABSTRACT: TGF-b is an immune regulatory cytokine central to immune homeostasis, tolerance, and autoimmunity. As a major suppressor, how SKI is involved in the fundamental roles of TGF-β in suppressing T cell function in autoimmunity and self-tolerance remains unknown. Here, we found that SKI protein was increased in activated T cells while decreased in response to exogenous and endogenous TGF-β, indicating a counter-balance role for SKI and TGF-β in activated T cells. Indeed, not only SKI deletion in T cells led to ameliorated spontaneous lethal autoimmune disease in mice with T-cell-specific deletion of TGFβRII, but also mitigated experimental autoimmune encephalomyelitis (EAE). Further investigation revealed that SKI deletion caused reduced T cell proliferation and related molecular programs even without TGF-β signaling, associating with enhanced TGF-β-related molecular program. This reveals a previously unappreciated SKI-dependent mechanism of TGF-β signaling in T cells besides current paradigm to explain how TGF-β restricts autoimmunity and bolsters tolerance.

ORGANISM(S): Mus musculus

PROVIDER: GSE303663 | GEO | 2026/07/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SKI is critical to counter TGF-β signaling to promote T cell function and autoimmunity

Project description:SKI is critical to counter TGF-β signaling to promote T cell function and autoimmunity

| PRJNA1296863 | ENA

Reversing SKI–SMAD4-mediated suppression is essential for TH17 cell differentiation

Project description:Disruption of Ski/Smad4 license Th17 differentiation. TGF-b-Ski-Smad4-RORgt-Th17 axis

2017-10-25 | GSE101527 | GEO

Reversing SKI–SMAD4-mediated suppression is essential for TH17 cell differentiation [ChIP-seq]

Project description:Disruption of Ski/Smad4 license Th17 differentiation. TGF-b-Ski-Smad4-RORgt-Th17 axis

2017-10-25 | GSE101593 | GEO

The Transcriptional Cofactor SKI Regulates Medullary Thymic Epithelial Cell Differentiation and Peripheral T Cell Responses

Project description:The thymus is an important site for the establishment and maintenance of an appropriate immune response through positive and negative selection of developing T cells. During selection, developing T cells interact with cortical and medullary thymic epithelial cells (TECs), termed cTECs and mTECs respectively. Our lab found that TEC-specific deletion of Ski decreased the mTEC compartment in the thymus and that tissue restricted antigen (TRA) expression in mTECs was also altered. Interestingly, these mice were significantly protected from developing experimental autoimmune encephalomyelitis (EAE) disease compared to the control mice and naïve CD4 T cells purified from Ski-deleted mice showed a defect in proliferation in vitro after global T cell receptor (TCR) stimulation. Overall, our findings suggest that SKI signaling in the thymus regulates mTEC differentiation and function as well as downstream peripheral T cell responses and provide evidence for targeting SKI in T cell driven autoimmune diseases such as multiple sclerosis.

2024-06-26 | GSE220665 | GEO

Cistrome analysis of SKI and RUNX1 in HL60

Project description:SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here we use ChIP-seq and RNA-seq to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which nearly 50% harbour SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI deletion causes a release of the myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets. RUNX1 ChIP-seq demonstrates that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 co-occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time on a genome-wide scale the predominant co-repressive function of SKI in AML cells and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.

2018-02-07 | GSE107553 | GEO

SKI-dependent TGFb signaling dictates CD103 expression in CD8+ T cells (ChIP-seq)

Project description:Initially identified as a functional marker for resident-memory (Trm) CD8+ T cells, CD103 (encoded by ITGAE gene) has broad roles in immunity and diseases. Elucidating the function and regulation of CD103 is thus of importance. This study revealed that the CD103 expression by CD8 T cells under steady state contributes to the clearance of acute viral infection. More importantly, it discovered TGF-SKI-Smad4 a critical signaling axis in restricting CD103 expression in CD8+ T cells for their function. Mechanistically, by ChIP-Seq and ChIP analysis, SKI associated with Smad4 was found to directly and epigenetically suppress CD103 transcription. This study therefore reveals a novel TGF-SKI-Smad4 pathway to specifically enable CD103 expression in CD8+ T cells for protective immunity.

2020-07-28 | GSE135533 | GEO

Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-ÃŽÂ² responses through SKI stabilization

Project description:Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-ÃŽÂ² signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-ÃŽÂ² signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This results in stabilization of SKI and consequently attenuation of TGF-ÃŽÂ² responses, in both knockin cells expressing an SGS mutation, and in fibroblasts from SGS patients. Thus, we reveal that SGS is associated with an attenuation of TGF-ÃŽÂ²-induced transcriptional responses, and not enhancement, which has important implications for other Marfan-related syndromes.

| EGAS00001004908 | EGA

SK-NEP-1 treated with SKI-5C

Project description:Wilm’s tumor(WT) is the most common malignant renal tumor in children, representing approximately 6-14% of all childhood cancers and about 95% of all pediatric renal malignancies. SKI-5C is a newly developed Sphk1 inhibitor. This small molecular inhibitor was firstly reported at 2009 by Wang et al. This study investigated the antitumor activity of SKI-5C in SK-NEP-1 cells. SKI-5C inhibited cell proliferation of SK-NEP-1 cells in a dose-dependent manner. Annexin V, Tunel and Hochest 33342 staining analysis showed that SKI-5C-treated cells showed more apoptotic features compared with the control.

2016-12-31 | GSE72980 | GEO

Transcriptome analysis of SKI knock-out in HL60 cells

Project description:Whole transcriptome for SKI knock-out and control HL60 cells was sequenced. SKI control and knockout samples were compared to find differentially expressed genes. Differentially expressed genes were further analysed to find the significance of SKI in HL60 cells.

2018-02-07 | GSE107555 | GEO

Sex Bias in CNS Autoimmune Disease Mediated by Androgen Control of Autoimmune Regulator

Project description:Male gender is protective against multiple sclerosis and other T cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well-understood. Autoimmune Regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here, we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared to females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. RNA-seq comparison of male vs. female expression in mTEC cells. Pools of 10 mice each were used for each replicate (two for male and two for female)

2016-03-09 | E-GEOD-79014 | biostudies-arrayexpress

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