Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling.

ABSTRACT: MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly been established that miRs influence the ontogeny of several immune cell lineages, the role of individual miRs during NK cell development has not been described. In this study, we show that miR-181 expression levels have a profound impact on the development of human NK cells from CD34(+) hematopoietic progenitor cells and IFN-? production in primary CD56(+) NK cells. We also demonstrate that nemo-like kinase (NLK), an inhibitor of Notch signaling, is a target of miR-181 in NK cells, and knockdown of NLK mirrors the developmental effect of miR-181 overexpression. We conclude that miR-181 promotes NK cell development, at least in part, through the suppression of NLK, providing an important link between miRs and Notch signaling.

SUBMITTER: Cichocki F

PROVIDER: S-EPMC3237765 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling.

Cichocki Frank F Felices Martin M McCullar Valarie V Presnell Steven R SR Al-Attar Ahmad A Lutz Charles T CT Miller Jeffrey S JS

Journal of immunology (Baltimore, Md. : 1950) 20111114 12

MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly been established that miRs influence the ontogeny of several immune cell lineages, the role of individual miRs during NK cell development has not been described. In this study, we show that miR-181 expression levels have a profound impact on the development of human NK cells from CD34(+) hematopoietic progenitor cells and IFN-γ production in primary ...[more]

PMID: 22084432

Similar Datasets

Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells.

Project description:The mechanisms underlying lymphocyte lineage stability and plasticity remain elusive. Recent work indicates that innate lymphoid cells (ILC) possess substantial plasticity. Whereas natural ILC2 (nILC2) produce type-2 cytokines, plastic inflammatory ILC2 (iILC2) can coproduce both type-2 cytokines and the ILC3-characteristic cytokine, IL-17. Mechanisms that elicit this lineage plasticity, and the importance in health and disease, remain unclear. In this study we show that iILC2 are potent inducers of airway inflammation in response to acute house dust mite challenge. We find that Notch signaling induces lineage plasticity of mature ILC2 and drives the conversion of nILC2 into iILC2. Acute blockade of Notch signaling abolished functional iILC2, but not nILC2, in vivo. Exposure of isolated nILC2 to Notch ligands induced Rorc expression and elicited dual IL-13/IL-17 production, converting nILC2 into iILC2. Together these results reveal a novel role for Notch signaling in eliciting ILC2 plasticity and driving the emergence of highly proinflammatory innate lymphocytes.

| S-EPMC5321819 | biostudies-literature

MicroRNA-34a suppresses colorectal cancer metastasis by regulating Notch signaling.

Project description:Dysregulation of microRNA (miRNA/miR) expression is causally associated with cancer initiation and progression. However, the precise mechanisms by which dysregulated miRNAs induce colorectal tumorigenesis remain unknown. In the present study, downregulation of miR-34a was identified in colorectal cancer cell lines and clinical specimens. Clinical studies revealed that miR-34a expression was negatively associated with distant metastasis, and positively associated with differentiation and survival of human colorectal cancer specimens. In vitro miRNA functional assays demonstrated that miR-34a bound to the putative 3'-untranslated regions of Notch1 and Jagged1 in SW480 cells, and thereby attenuated the migration and invasion of the colon cancer cells. It was additionally identified that miR-34a downregulated the expression of vimentin and fibronectin via Notch1 and Jagged1. Overall, these data indicate that miR-34a serves a key role in suppressing colorectal cancer metastasis by targeting and regulating Notch signaling.

| S-EPMC5530141 | biostudies-other

Cutting edge: NK cell licensing modulates adhesion to target cells.

Project description:Binding of NK cell inhibitory receptors to MHC class I (MHC-I) confers increased responsiveness to NK cells by a process known as NK cell licensing/education. Reduced MHC-I expression or a lack of inhibitory receptors for MHC-I results in diminished NK cell responsiveness. In this study, we evaluated the effect of human and mouse NK cell licensing on early stages of natural cytotoxicity. Unlicensed NK cells did not form as many stable conjugates with target cells. The reduction of NK cell conjugation to target cells was not attributed to altered ?2 integrin LFA-1 properties but was instead due to reduced inside-out signaling to LFA-1 by activating receptors. For those unlicensed NK cells that did form conjugates, LFA-1-dependent granule polarization was similar to that in licensed NK cells. Thus, licensing controls signals as proximal as inside-out signaling by activating receptors but not integrin outside-in signaling for granule polarization.

| S-EPMC3795972 | biostudies-literature

Cutting Edge: STAT1-Mediated Epigenetic Control of <i>Rsad2</i> Promotes Clonal Expansion of Antiviral NK Cells.

Project description:NK cells represent a cellular component of innate immunity but possess features of adaptive immunity, including clonal expansion and establishment of long-lived memory following infection. During mouse CMV (MCMV) infection, we observed Rsad2 (which encodes Viperin) to be among the most highly induced IFN stimulatory genes in activated NK cells, correlating with increased chromatin accessibility at the Rsad2 gene locus. Furthermore, in NK cells stimulated with IFN-α, the promoter region of Rsad2 was enriched for STAT1 binding and the permissive histone mark H3K4me3. IFN-αR- and STAT1-deficient NK cells showed an impairment of Rsad2 induction and chromatin accessibility during MCMV infection. Finally, Rsad2-deficient NK cells were defective in clonal expansion and memory formation following exposure to MCMV, in part because of greater apoptosis. Thus, our study reveals a critical mechanism of STAT1-mediated epigenetic control of Rsad2 to promote the adaptive behavior of NK cells during viral infection.

| S-EPMC7314649 | biostudies-literature

Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage.

Project description:Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK cells (cNKs). All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNKs additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK development. Formation of the entire lymphoid and nonlymphoid type 1 ILC compartment appears to require the semiredundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes induces cNK-like properties across the lymphoid and nonlymphoid type 1 ILC compartments. Subsequent to their divergent lineage specification, hILC1s and cNKs thus possess substantial developmental plasticity.

| S-EPMC4744497 | biostudies-literature

Cutting Edge: Human CD49e- NK Cells Are Tissue Resident in the Liver.

Project description:Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e- NK cells are tissue resident in the liver. Thus, these studies indicate that tissue-resident NK cells are evolutionarily conserved in humans and mice, providing a foundation to explore their role in human disease.

| S-EPMC5296254 | biostudies-literature

Cutting edge: antibody-dependent memory-like NK cells distinguished by FcR? deficiency.

Project description:Because NK cells lack gene-recombination machinery and are thought to be relatively short-lived, it is unclear whether NK cells can mount long-term effective recall responses to reinfections by diverse pathogens. In this article, we report that FcR?-deficient NK cells, which we recently identified and termed g(-)NK cells, possess distinct memory features directed by FcR-mediated Ab-dependent target recognition. The presence of g(-)NK cells was associated with prior human CMV (HMCV) infection, yet g(-)NK cell responses were not restricted to HCMV-infected target cells. In the presence of virus-specific Abs, g(-)NK cells had greatly enhanced functional capabilities, superior to conventional NK cells, and were highly responsive to cells infected with either HCMV or HSV-1. Remarkably, the g(-)NK cell subset persisted long-term at nearly constant levels in healthy individuals. Therefore, FcR? deficiency distinguishes an Ab-dependent memory-like NK cell subset with enhanced potential for broad antiviral responses.

| S-EPMC3623944 | biostudies-literature

Cutting edge: IL-15-independent NK cell response to mouse cytomegalovirus infection.

Project description:NK cells respond rapidly during viral infection. The development, function, and survival of NK cells are thought to be dependent on IL-15. In mice lacking IL-15, NK cells are found in severely decreased numbers. Surprisingly, following infection of IL-15- and IL-15Ralpha-deficient mice with mouse CMV, we measured a robust proliferation of Ly49H-bearing NK cells in lymphoid and nonlymphoid organs capable of cytokine secretion and cytolytic function. Remarkably, even in Rag2(-/-) x Il2rg(-/-) mice, a widely used model of NK cell deficiency, we detected a significant number of NK cells 1 wk after mouse CMV infection. In these mice we measured a >300-fold expansion of NK cells, which was dependent on recognition of the m157 viral glycoprotein ligand and IL-12. Together, these findings demonstrate a previously unrecognized independence of NK cells on IL-15 or other common gamma signaling cytokines during their response against viral infection.

| S-EPMC2745285 | biostudies-literature

Notch signaling controls liver development by regulating biliary differentiation.

Project description:In the mammalian liver, bile is transported to the intestine through an intricate network of bile ducts. Notch signaling is required for normal duct formation, but its mode of action has been unclear. Here, we show in mice that bile ducts arise through a novel mechanism of tubulogenesis involving sequential radial differentiation. Notch signaling is activated in a subset of liver progenitor cells fated to become ductal cells, and pathway activation is necessary for biliary fate. Notch signals are also required for bile duct morphogenesis, and activation of Notch signaling in the hepatic lobule promotes ectopic biliary differentiation and tubule formation in a dose-dependent manner. Remarkably, activation of Notch signaling in postnatal hepatocytes causes them to adopt a biliary fate through a process of reprogramming that recapitulates normal bile duct development. These results reconcile previous conflicting reports about the role of Notch during liver development and suggest that Notch acts by coordinating biliary differentiation and morphogenesis.

| S-EPMC2673761 | biostudies-literature

Cutting Edge: IL-1 Receptor Signaling is Critical for the Development of Autoimmune Uveitis.

Project description:IL-1? is a proinflammatory cytokine important for local and systemic immunity. However, aberrant production of this cytokine is implicated in pathogenic mechanisms of a number of inflammatory diseases, including Behçet's disease and age-related macular degeneration. In this study, we report the increased secretion of IL-1? in the retina by neutrophils, macrophages, and dendritic cells during ocular inflammation and show that loss of IL-1R signaling confers protection from experimental autoimmune uveitis. Moreover, the amelioration of experimental autoimmune uveitis in Il1r-deficient mice was associated with reduced infiltration of inflammatory cells into the retina and decreased numbers of uveitogenic Th17 cells that mediate uveitis. These findings indicate the possible utility of IL-1R-blocking agents for the treatment of ocular inflammatory diseases.

| S-EPMC4707108 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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