RNA-seq data of ABC from Bm12-induced lupus model
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Mus musculus
SUBMITTER: Nan Shen
PROVIDER: E-MTAB-12568 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Thymi from Foxn1cre x ROSA26TdTOMATO were enzymaticaly digested, cells were MACS enriched for CD11c+ fraction. Dendritic cells were then FACS sorted (BD influx sorter) as Gr-1-CD11c+TdTOMATO+. TdTOMATO DCs represent fraction of thymic DCs which acquire antigen (TdTOMATO) from thymic epithelial cells, through the process of antigen transfer.
2020-03-20 | E-MTAB-8028 | biostudies-arrayexpress
Project description:B cell tolerance is established using deletion, anergy and receptor editing mediated by secondary recombination but it is unclear why autoreactive B cells choose a tolerance mechanism over another. We identified subgroups of patients with either rheumatoid arthritis or common variable immunodeficiency who presented defects in secondary recombination, which correlated with unusual CD21-/lo naïve B cells in their blood. CD21-/lo B cells were unable to induce calcium flux, get activated or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these B cells are anergic. Moreover, CD21-/lo B cells are often autoreactive and may express anti-nuclear antibodies. Thus, anergy can be a default tolerance mechanism mainly induced when receptor editing fails to silence developing autoreactive B cells. Experiment Overall Design: RNA was extracted from batch sorted CD19+CD21+CD10-CD27- and CD19+CD21-CD10-CD27- naïve B cells isolated from donors using the Absolutely RNA microprep kit (Stratagene). 100-200 ng of RNA was obtained per sample, and the quality of the purified RNA was assessed by the Bioanalyzer from Agilent. Using the Ovation biotin system kit from Nugen, 30-50ng of RNA was amplified and labeled to produce cDNA. Labeled cDNA was hybridized on chips containing the whole human genome (Human Genome U133 2.0 from Affymetrix). Data from CD21+ and CD21- B cell populations were compared in order to determine the gene signature of the newly described CD21- B cells.
2009-12-04 | E-GEOD-13917 | biostudies-arrayexpress
Project description:Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy (AI) is an approach that involves administration of antiviral T cells and has shown promise in clinical studies for the treatment of peripheral virus infections in humans such as cytomegalovirus, Epstein-Barr virus, and adenovirus, among others. Clearance of neurotropic infections, on the other hand, is particularly challenging because the central nervous system (CNS) is relatively intolerant of immunopathological reactions. Therefore, it is essential to develop and mechanistically understand therapies that noncytopathically eradicate pathogens from the CNS. Here, we used mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV) to demonstrate that therapeutic antiviral T cells can completely purge the persistently infected brain without causing blood brain barrier breakdown or tissue damage. Mechanistically, this is accomplished through a tailored release of chemoattractants that recruit antiviral T cells, but few pathogenic innate immune cells such as neutrophils and inflammatory monocytes. Upon arrival, T cells enlisted the support of nearly all brain resident myeloid cells (microglia) by converting them into CD11c+ antigen-presenting cells (APCs) – a cell population also found in the brain of a human immunodeficiency virus infected patient. Two-photon imaging studies revealed that antiviral CD8+ and CD4+ T cells interacted directly with CD11c+ microglia and induced STAT1 signaling, but did not initiate programmed cell death. We propose that noncytopathic CNS viral clearance can be achieved by therapeutic antiviral T cells reliant on restricted chemoattractant production and interactions with apoptosis-resistant microglia. 6 Mouse Microglia-sorted Brain Samples: 3 (-) AI, 3 (+) AI.
2015-06-22 | E-GEOD-66421 | biostudies-arrayexpress
Project description:Fibroblastic reticular cells (FRCs) (CD45- Ter119-MADCAM1- CD21/35- CD31- PDPN-) from skin draining lymph nodes of Grem1-Cre-ERT2.cki; Rosa26-LSL-EYFP mice were sorted and subjected to bulk RNA-seq of Grem1 reporter + and Grem1 reporter - cells.
2021-04-10 | E-MTAB-10205 | biostudies-arrayexpress
Project description:The complex relationship between Th1 and Th17 cells is incompletely understood. The transcription factor T-bet is best known as the master regulator of Th1 lineage commitment. However, attention is now focused on the repression of alternate T cell subsets mediated by T-bet, particularly the Th17 lineage. Specifically it has recently been suggested that pathogenic Th17 cells express T-bet and are dependent on IL-23. However, T-bet has previously been shown to be a negative regulator of Th17 cells. We have taken an unbiased approach to determine the functional impact of T-bet on Th17 lineage commitment. Genome-wide analysis of functional T-bet binding sites provides an improved understanding of the transcriptional regulation mediated by T-bet, and suggests novel mechanisms by which T-bet regulates T helper cell differentiation. Specifically, we show that T-bet negatively regulates Th17 lineage commitment via direct repression of the transcription factor interferon regulatory factor-4 (IRF4). An in vivo analysis of the pathogenicity of T-bet deficient T cells demonstrated that Th17 responses were augmented in the absence of T-bet, and we have defined a critical temporal window for T-bet function. The interaction of the two key transcription factors T-bet and IRF4 during the determination of T cell fate choice significantly advances our understanding of the mechanisms underlying the development of pathogenic T cells. ChIP-seq analysis of T-bet in WT and Tbet -/- mice.
2013-12-03 | E-GEOD-40623 | biostudies-arrayexpress
Project description:We applied Illumina massively parallel signature sequencing to identify miRNomes in CD11c+Ia high and CD11c+Ia low cells.The miRNomes of these DC subsets will contribute to investigate the significance of miRNAs in DC immunobiology. Examination of miRNome in CD11c+Ia high and CD11c+Ia low cells . All two mouse cell types.
2015-06-16 | E-GEOD-51574 | biostudies-arrayexpress
Project description:Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to BRD4 and other proteins of the BET (bromodomain and extra-terminal domain) family, was previously shown to suppress the production of pro-inflammatory proteins by macrophages and block acute inflammation in mice. Here we investigate the effect of I-BET-762 on T cell function. We show that treatment of naïve CD4+ T cells with I-BET-762 during early differentiation modulates subsequent cytokine production, and inhibits the ability of Th1-skewed cells to induce autoimmune pathogenesis in a model of experimental autoimmune encephalomyelitis (EAE) in vivo. The suppressive effects of I-BET-762 on T-cell mediated inflammation were not due to inhibition of expression of the pro-inflammatory cytokines, IFN-. or IL-17, but correlated with the ability to suppress GM-CSF production from CNS-infiltrating T cells, resulting in decreased recruitment of macrophages and granulocytes. The effects of I-BET-762 were distinct from those of the fumarate ester, dimethyl fumarate (DMF), a candidate drug for treatment of multiple sclerosis (MS). Our data suggest that I-BET and DMF could have complementary roles in the treatment of MS, and provide a strong rationale for inhibitors of BET-family proteins in the treatment of autoimmune diseases, based on their dual ability to suppress granulocyte and macrophage recruitment by T cells as well as production of pro-inflammatory proteins by macrophages. RNA from resting or activated CD4+ T cells grown in the presence of a control substance (DMSO or Control-768) or two different concentrations of I-BET-762, was hybridized to the chip. There are 3 biological replicates for a total of 2 (cell states) x 4 (conditions) x 3 (replicates) = 24 samples.
2012-08-03 | E-GEOD-39886 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE22127: Expression profiling of small intestine lamina propria dendritic cells GSE22128: Expression profiling of splenic dendritic cells Dendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) and compared it to splenic DCs (CD11c+ DC), from mice. We sought to determine the unique genetic profile of small intestine lamina propria CD11c+ cells compared to splenic CD11c+ cells. We performed a meta-analysis using the expression profiles of Intestinal lamina propria CD11c+ CD11b+ DCs (GSM550122), Intestinal lamina propria CD11c+ CD11b- DCs (GSM550121) and Splenic CD11c+ DCs (GSM550126). This study combined and re-normalized the microarray data from GSE22127 and GSE22128 studies. Refer to individual Series for additional details
2010-06-16 | E-GEOD-22136 | biostudies-arrayexpress
Project description:Age/autoimmune-associated B cells (ABCs) are a T-bet dependent B cell subset, which accumulates prematurely in autoimmune settings. The molecular pathways that regulate ABCs in autoimmunity are largely unknown. The SWEF proteins include SWAP-70 and DEF6, a newly identified SLE risk variant. SWEF-deficient mice (double knock-out=DKO) develop a lupus like syndrome, which is accompanied by a marked expansion of ABCs. The accumulation of ABCs in DKO mice provided us with a unique opportunity to gain new insights into the molecular features that characterize the ABCs that prematurely expand in autoimmune conditions. Splenic Follicular B cells (FoB, B220+CD19+CD23+CD11c-CD11b-) and ABCs (B220+CD19+CD11c+CD11b+) were FACS sorted from >20 weeks old WT or DKO female mice and RNA-seq was employed to compare the transcriptome of DKO ABCs to that of FoB cells derived from either WT or DKO mice. Here we show that loss of SWEF proteins leads to altered gene expression in B cells independently of their differentiation state. In addition, a subset of genes was uniquely regulated in ABCs from DKO mice as compared to FoB cells from either WT or DKO mice. Ananlysis of the ATAC-seq experiment show that the ABCs that expand aberrantly in the DKO autoimmune setting exhibit a unique chromatin landscape and ABC-specific accessible loci displayed enrichment in AP-1/BATF, IRF, and T-bet binding motifs. Together our findings suggest that absence of SWEF proteins affects several key processes in ABCs. In particular, we observed alterations in a number of pathways involved in the control of cellular proliferation and inflammation, a finding that may play a crucial role in the premature accumulation of ABCs in DKOs and could distinguish them from non-autoimmune ABCs.
2018-03-01 | GSE99480 | GEO
Project description:Dendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) from mice. Keywords: Lamina propria, DCs, cell type comparison We sought to determine the expression profile of small intestine lamina propria CD11c+ cells. RNA was extracted from DCs sorted from mouse small intestine (CD11c+CD11b- and CD11c+CD11b+ cells) and hybridized on Affymetrix microarrays.
2010-06-16 | E-GEOD-22127 | biostudies-arrayexpress