Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA496482 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8056651_1.fastq.gz | Fastqsanger.gz | |||
| SRR8056651_2.fastq.gz | Fastqsanger.gz | |||
| SRR8056652_1.fastq.gz | Fastqsanger.gz | |||
| SRR8056652_2.fastq.gz | Fastqsanger.gz | |||
| SRR8056653_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Regulatory T (Treg) cells play central roles in maintaining immune homeostasis and self-tolerance. However, the molecular mechanisms underlying Treg cell homeostasis and suppressive function are still not fully understood. Here, we report that the deletion of another P subfamily members of the forkhead box (Foxp) subfamily member Foxp1 in Treg cells led to increased numbers of activated Treg (aTreg) cells at the expense of quiescent Treg cells, and also resulted in impaired Treg suppressive function. Mice with Foxp1-deficient Treg cells developed spontaneous inflammatory disease with age; they also had more severe inflammatory disease in colitis and experimental autoimmune encephalomyelitis (EAE) models. Mechanistically, we found that Foxp1 bound to the conserved noncoding sequence 2 (CNS2) element of the Foxp3 locus and helped maintain Treg suppressive function by stabilizing the Foxp3 expression. Furthermore, we found that Foxp1 and Foxp3 coordinated the regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression levels. Taken together, our study demonstrates that Foxp1 plays critical roles in both maintaining Treg cell quiescence during homeostasis and regulating Treg suppressive function.
2019-04-10 | GSE121251 | GEO
Project description:Regulatory T (Treg) cells play central roles in maintaining immune homeostasis and self-tolerance. However, the molecular mechanisms underlying Treg cell homeostasis and suppressive function are still not fully understood. Here, we report that the deletion of another P subfamily members of the forkhead box (Foxp) subfamily member Foxp1 in Treg cells led to increased numbers of activated Treg (aTreg) cells at the expense of quiescent Treg cells, and also resulted in impaired Treg suppressive function. Mice with Foxp1-deficient Treg cells developed spontaneous inflammatory disease with age; they also had more severe inflammatory disease in colitis and experimental autoimmune encephalomyelitis (EAE) models. Mechanistically, we found that Foxp1 bound to the conserved noncoding sequence 2 (CNS2) element of the Foxp3 locus and helped maintain Treg suppressive function by stabilizing the Foxp3 expression. Furthermore, we found that Foxp1 and Foxp3 coordinated the regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression levels. Taken together, our study demonstrates that Foxp1 plays critical roles in both maintaining Treg cell quiescence during homeostasis and regulating Treg suppressive function.
| S-EPMC6534289 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSC) are potent negative regulators of immune responses at many pathological conditions. It is widely accepted that these cells are not present under steady state condition. Here, we report that MDSC with highly potent ability to suppress T cells accumulate during first two weeks of life in mice. MDSC suppressive activity in neonates was triggered by lactoferrin, a component of milk, and mediated by nitric oxide and up-regulation of PGE2 regulated by S100A9/A8 proteins. Newborn MDSC had transcriptome similar to that of tumor MDSC. However, they had strong up-regulation of antimicrobial gene network. This was associated with enhanced antimicrobial activity of these cells. MDSC played a critical role in control of experimental necrotizing enterocolitis in newborn mice. In humans, MDSC in cord blood of low-weight preterm infants prone to the development of NEC had significantly lower suppressive activity than the cells from cord blood of infants with normal weight. Thus, transitory presence of MDSC after birth is critical for the maintenance of immune homeostasis.
2018-01-03 | GSE97993 | GEO
Project description:Alpha4 is Critical for Adipocyte Maintenance and Mitochondrial Homeostasis through Regulation of Insulin Signaling
| PRJNA865656 | ENA
Project description:Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown. We propose to determine the roles for Foxp1/4 in lung development by deleting these genes in lung epithelial specific knockout mice. To explore the genome wide consequences of Foxp1/4 deficiency on secretory epithelial differentiation in the lung, we performed microarray analysis of Shh- cre control and Foxp1/4ShhcreDKO mutants lungs at E14.5, 3 embryos, respectively.
2012-08-01 | E-GEOD-34584 | biostudies-arrayexpress
Project description:FOXP3+ Treg cells are critical for immune tolerance. Genetic deletion of the Forkhead domain containing proteins of the FOXP-subfamily member FOXP1 from Tregs results in impaired function associated with reduced CD25 expression and IL-2 signaling, but to date the only other FOXP family member expressed in Tregs, FOXP4, has been minimally studied. To investigate the potential functional interactions among FOXP family members in Treg cells, we specifically deleted Foxp1, Foxp4 or both in FOXP3+ committed Treg cells in mice. Our findings show that mice with combined, but not individual, deficiency in FOXP1 and FOXP4 exhibit lymphoproliferation, inflammation, autoimmunity, and early lethality. The combined absence of FOXP1 and FOXP4 in Tregs results in an activated/effector-like phenotype with compromised suppressive function in peripheral lymphoid organs, an enhanced germinal center response and proinflammatory cytokine production. We further show that FOXP1 and FOXP4 bind to Il2ra promoter regions to regulate CD25 expression in Tregs. Through pairwise comparison among mouse strains with Treg-specific deletion of Foxp1, Foxp4 or both, our findings indicate a non-redundant but insufficient role of FOXP4 in Treg cell function.
2025-07-08 | GSE300286 | GEO
Project description:High expression of the FOXP1 transcription factor distinguishes the highly aggressive Activated B Cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL) from the more indolent Germinal Center (GCB) DLBCL subtype and is correlated with poor prognosis. A genetic or functional role for FOXP1 in lymphomagenesis and/or tumor maintenance, however, remains unknown. Here, we report that sustained expression of FOXP1 is necessary for ABC DLBCL cell line survival. Genome-wide transcript profiling reveals that FOXP1 acts directly and indirectly by enforcing expression of known ABC DLBCL hallmarks, including the classical NF-kappaB survival pathway. Our data further suggest that FOXP1 maintains the ABC subtype distinction by repressing gene expression programs dominant in GCB DLBCL and supports a model in which the target of ABC DLBCL transformation is a transitory cell type en route from the germinal center B cell to the terminally differentiated plasma cell.
2015-12-01 | GSE64586 | GEO
Project description:Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown. We propose to determine the roles for Foxp1/4 in lung development by deleting these genes in lung epithelial specific knockout mice.
2012-08-02 | GSE34584 | GEO
Project description:We demonstrate that Prnp dosage is critical for the maintenance of neuronal homeostasis since both its absence and, more relevantly, its overexpression induce higher sensitivity to kainate (KA) damage. These data correlate with electrophysiological results in freely behaving mutant mice showing an imbalance in activity-dependent synaptic processes, as determined from input/output curves, paired-pulse facilitation, and LTP studies. Gene expression profiling showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission among others were co-regulated in knockout and PrPc overexpressing mice. RT-qPCR analysis of neurotransmission-related genes confirmed GABA-A and AMPA-Kainate receptor subunit transcriptional co-regulation in both Prnp -/- and Tg20 mice. Our results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its interactions with GABAA and AMPA-Kainate receptors. Keywords: steady state expression; adult brain tissue; hippocampus; genetic modification; transgenic gain of function mutation; targetted deletion loss of function mutation We performed a global transcriptome analysis of three strains that differ in their Prnp gene dose using Illumina Sentrix 6 mouse v1.1 beadarrays. We analyzed mRNA expression in the hippocampi of four individual male mice from each of three strains: 1) Tg20, with a 30 exogenous copies of the Prnp gene within a Prnp -/- background that overexpresses PrPc about 6-7 times the normal wild type levels; 2) littermates lacking the transgene and therefore carrying only the homozygous knock out Prnp -/- strain which lacks expression of PrPc; and 3) their wild type counterparts carrying two copies of the intact Prnp gene and expressing normal levels of PrPc
2010-04-09 | E-GEOD-16223 | biostudies-arrayexpress
Project description:Iron metabolism has emerged as a critical factor in cell viability, both in normal and pathological contexts. However, the intricate relationship between iron metabolism and the maintenance of adult stem cells and cancer stem cells remains incompletely understood. The ferritin complex, responsible for intracellular iron storage and buffering, plays a pivotal role in this process. Our research provides insights into the regulatory role of ferritin-mediated iron homeostasis in hematopoietic stem cells (HSCs).
2024-04-17 | GSE240742 | GEO