Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation

ABSTRACT: Transcription factors specialized to limit the destructive potential of inflammatory immune cells remain ill-defined. We discovered loss-of-function variants in the X-linked ETS transcription factor gene ELF4 in multiple unrelated male patients with early-onset mucosal autoinflammation and inflammatory bowel disease (IBD) characteristics including fevers and ulcers that responded to IL-1, TNF, or IL-12p40 blockade. Using cells from patients and two newly generated mouse models, we uncovered hyperinflammatory responses of ELF4-mutant macrophages to a range of innate stimuli. Mechanistically, Elf4 in macrophages both sustained expression of anti-inflammatory genes such as Il1rn and limited upregulation of inflammation amplifiers, including S100A8, Lcn2, Trem1, and neutrophil chemoattractants. Indeed, therapeutic Trem1 blockade reversed inflammation and intestine pathology in Elf4-mutant mice challenged with lipopolysaccharide in vivo. Thus, the ELF4 transcription factor restrains inflammation and protects against mucosal disease, a discovery with broad translational relevance for human inflammatory diseases such as IBD.

ORGANISM(S): Mus musculus

PROVIDER: GSE175569 | GEO | 2021/07/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression signatures for ELF4

Project description:To elucidate how ELF4 confers anti-growth activity, gene expression profiles were compared between wildtype- and mutant-expressing T3M-1 Cl-10 cells with the use of DNA microarrays. T3M-1 Cl-10 cells were infected with a mock retrovirus or virus generated from pMXS-ires-EGFP expressing ELF4 or ELF4(L211M), and EGFP?positive fractions were purified with a cell sorter. Thus gene expression profiling of purely mock/ELF4/ELF4(L211M)-expressing cells was performed with SurePrint G3 Human Gene Expression 8×60K v2 Microarray.

2013-12-04 | E-GEOD-52855 | biostudies-arrayexpress

Genome-wide screening for ELF4-binding sites.

Project description:ELF4 (also known as MEF) is a member of the ETS family of transcriptional factors. While an oncogenic role has been demonstrated for ELF4 mainly in hematopoietic malignancies, its definitive function in human carcinogenesis is not clear yet. Here we demonstrate that a wide array of human tumors carry somatic, loss-of-function mutations in ELF4 for its transcriptional activity, and restoring its function exerts anti-proliferative effects. To further explore the tumor suppressive function of ELF4, its binding sites were searched among the human genome with the use of chromatin immunoprecipitation coupled with sequencing (ChIP-seq). Examination of binding site for FLAG-immunoprecipitated mock, ELF4 (WT) and ELF4 (L211M) with each input sample as a control.

2016-03-01 | E-GEOD-53357 | biostudies-arrayexpress

Genome-wide screening for ELF4-binding sites.

2016-03-01 | GSE53357 | GEO

Gene expression signatures for ELF4

2013-12-04 | GSE52855 | GEO

Cyclin-dependent kinase 9 is a therapeutic target for anti-TNF resistant inflammatory bowel disease

Project description:The treatment of auto-inflammatory diseases is often limited by resistance to single cytokine blockade, primarily anti-TNF antibodies. This is a particularly important cause of treatment failure in inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis and is genetically linked to mucosal inflammation by causal variation in its binding sites. However, transcription factors such as T-bet are difficult to target therapeutically. Using CDK9 inhibitors, we show that modulation of P-TEFb (cyclinT1/CDK9), a transcriptional elongation factor downstream of T-bet, potently represses genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targets genes that are highly expressed in anti-TNF resistant IBD and that predict non-response to anti-TNF therapy. Collectively, our findings reveal CDK9 as a potential target in anti-TNF resistant IBD, which has the potential for rapid translation to the clinic.

2022-06-17 | GSE172372 | GEO

Single-cell census of the colonic epithelium reveals goblet cell drivers of barrier breakdown in inflammatory bowel disease

Project description:Colonic epithelial cells facilitate host-microbe interactions to control mucosal immunity, and they also coordinate recycling and forming the mucus barrier. Epithelial barrier breakdown underpins inflammatory bowel disease (IBD). However, we do not know the specific contributions of each epithelial cell subtype to this process. Here, we profiled single colonic epithelial cells in health and IBD. Our results identified previously unknown subtypes and crypt gradients of progenitors, colonocytes and goblet cells. We also revealed a novel specialized metal ion storage and chloride secretory cell. In IBD, we discovered a unique cluster of disease associated goblet cells that remodels the barrier. We found downregulated WFDC2, a novel goblet cell expressing anti-protease that inhibited bacterial growth. Our in vivo studies demonstrated WFDC2 preserved tight junction integrity and prevented commensal invasion and mucosal inflammation. We delineate markers and transcriptional states, identify a new colonic epithelial cell and uncover fundamental principles of epithelial plasticity and barrier breakdown in IBD. Thus, our study reveals new therapeutic targets and disease-related mechanisms in IBD

2019-02-16 | PXD011655 | Pride

RNA-seq of colon tissue from wild type and Elf4-/- mice with colitis

Project description:ELF4 is a transcription factor, and to identify its potential targets, the inflamed colons of wild type and Elf4 deficient mice were subjected to whole genome RNA sequencing.

2019-10-16 | GSE121305 | GEO

Human colon expression in healthy controls, colon-only CD, ileo-colonic CD, and UC

Project description:Colon gene expression in human IBD. The three major clinical subsets of Inflammatory Bowel Disease (IBD) include colon-only Crohn's Disease (CD), ileo-colonic CD, and Ulcerative Colitis (UC). These experiments tested differential colon gene expression in these three types of IBD, relative to healthy control samples, and the local degree of mucosal inflammation as measured by the CD Histological Index of Severity (CDHIS). Colon biopsy samples were obtained from IBD patients at diagnosis and during therapy, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, with a focus upon candidate genes identified in a recent genome wide association study in pediatric onset IBD. Data suggested that two of these candidate genes are up regulated in pediatric IBD, partially influenced by local mucosal inflammation. These experiments tested differential colon gene expression in healthy, CD, and UC samples for candidate genes identified in a recent pediatric onset IBD genome wide association study. Keywords: Single time point in CD and UC and healthy controls. Colon RNA was isolated from biopsies obtained from CD and UC at diagnosis and during therapy and healthy controls. Samples were obtained from the most proximal affected segment of colon. Microarray experiments were performed as described in the CCHMC microarray core, and data was analyzed as described above in the summary. The '107' internal control CEL files (for batches 1,2,3,4,5) used for normalization of the Sample VALUEs are also contained within this data set.

2009-03-10 | E-GEOD-10616 | biostudies-arrayexpress

Human colon expression in healthy controls, colon-only CD, ileo-colonic CD, and UC

2009-03-11 | GSE10616 | GEO

Human colon aspirate proteins analyzed by LC-MSMS

Project description:Colonic aspirates were collected at diagnostic colonoscopy from inflammatory bowel disease (IBD) and control, treatment-naive children. The colonic mucosal-luminal interface (MLI) proteomes were analyzed for 18 control and 42 IBD patients by liquid-chromatography mass spectrometry.

2018-03-19 | PXD006383 | 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