Transcription profiling of BXSB mice to study lupus erythematosus
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: unknown unknown
PROVIDER: E-MIMR-7 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Single-cell RNA-seq from CD4+ T lymphocytes from uninfected steady-state mouse, two mice with Salmonella typhimurium infection at day 14 and one mouse at day 49 post-infection. Used to demonstrate application of reconstruction and analysis of T cell receptor sequences from single-cell RNA-seq.
2016-03-06 | E-MTAB-3857 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is an autoimmune disorder with systemic inflammation, autoantibody accumulation and organ damage. The abnormalities of double-negative (DN) T cells are considered as an important commander of SLE. Neddylation, an important type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE remains largely unexplored. Here, we reported that neddylation inactivation with MLN4924 or genetic abrogation of Ube2m in T cells prevented SLE development for decreased DN T cell accumulation. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells for Fas mutation. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim interrupted the improvement of DN T cell apoptosis and the consequential relieved lupus symptoms for Ube2m KO. Our findings identified that neddylation inactivation promoted Bim-mediated apoptosis of DN T cells and prevented lupus progress. Clinically, we also found the percentages of DN T cells were improved accompanied with reduced apoptosis of DN T cells in SLE patients. Moreover, the neddylation of Cullin1 was higher while Bim level was decreased in SLE patients compared with healthy control. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Together, these findings provide the first evidence of the neddylation role in lupus development, suggesting a novel therapeutic strategy for lupus.
2024-01-26 | PXD045686 | Pride
Project description:CD44 wild-type and knockout C57 BL/6 mice were immunized by subcutaneous injection of MOG35-55 peptide. CD4 T cells were isolated from spleens of the mice on day 15 of the MOG35-55 peptide immunization. Peripheral blood lymphocytes (PBLs) were prepared from multiple sclerosis patients and normal individuals. Total RNA was extracted and subjected to microRNA high-throughput array with Affymetrix platform.
2012-05-01 | E-MEXP-3594 | biostudies-arrayexpress
Project description:Spleens from the B6 mice were isolated and single cell suspension was made. CD4 T cells were purified from the splenocytes using magnetic bead separation. Briefly, Splenocytes were incubated with biotinylated antibody cocktail consisting of antibodies (Biolegend) to CD19, B220, CD11b, CD11c, NK1.1, Gr1, CD25 CD8. After a wash step, cells were incubated with streptavidin conjugated magnetic particles (BD Biosciences). After washing, CD4 T cells were isolated by applying a magnetic field and removing the untouched cells. Purified CD4 T cells were then activated with plate-bound anti-CD3 plus anti-CD28 in presence of either Th1 or Th17 or Th1/17 polarizing condition for 3 days. Total RNA from the 3 days differentiated Th1, Th17 and Th1/17 cells was isolated using mirVana miRNA isolation Kit (Invitrogen).
2017-09-13 | E-MTAB-5237 | biostudies-arrayexpress
Project description:Microarray analysis was performed on BWF1 mice spleenocyte cells in control and pCONS treated mice. Microarray analysis identified many genes differentially expressed in control vs pCONS treated mice spleenocytes. Some of the genes were uperegulated and some of the genes were down regulated. Microarray analysis was performed in CD4, CD8, and whole spleenocyte WBC cells. Experiment Overall Design: RNA was isolated from the mice spleenocytes from control and pCONs treated mice one week after treatment.
2008-11-13 | E-GEOD-13364 | biostudies-arrayexpress
Project description:To investigate how HSCs functionally compensate for the B cell deficiencies of other HSCs within an organism, we co-transplanted wildtype (WT) HSCs and lineage-deficient HSCs into lethally irradiated WT recipient mice. WT HSCs were then purified from the bone marrow of recipient mice for RNA isolation and sequencing. The purpose is to determine whether there are common genes shared between compensating WT HSCs in the WT co-transplanted with uMT-/- (B6.129S2(B6)-Ighmtm1Cgn/J) and WT co-transplanted with NSG (NOD-scid IL2Rgamma null).
2018-06-14 | E-MTAB-6776 | biostudies-arrayexpress
Project description:T-cell receptor (TCR) signaling is essential for the function of T cells. Here we combine mouse genetics and affinity purification coupled to quantitative mass spectrometry to monitor the composition and dynamics of the signaling complexes that assemble around 15 nodes of the TCR signaling cascade of primary CD4+ T cells. This dataset contains the experiments performed with 14 different bait proteins • Cbl • Cblb • Fyb • Inpp5d • Itk • Lck • Lcp2 • Nck1 • Nfatc2 • Plcg1 • Ptpn22 • Ptpn6 • Themis • Vav1 Each of them contains mass spectrometry results from the analysis of AP-MS experiments, based on the endogenous expression of One-Strep-tagged (OST) bait proteins in engineered mice models, and affinity purification of these proteins from primary CD4+ T cells, using Streptactin beads. Purification of OST proteins was performed at 5 different time points of stimulation of CD4+ T cells with anti-CD3 and anti-CD4 antibodies (0s; 30s; 120s; 300s; 600s). Each AP-MS purification of an OST- protein is associated with a corresponding control (purification from WT CD4+ T cells) at the same time point of stimulation. Several biological replicate experiments (time course OST series + associated WT controls) were performed for each bait. Several MS replicates were acquired for each sample. In addition, we analyzed the total proteome of CD4+ T cells isolated from each engineered mice model (14 different mice expressing an OST bait) and from WT mice, in order to calculate copy numbers of the baits and their associated proteins.
2019-09-26 | PXD007660 | Pride
Project description:We analyzed the total proteome of CD4+ T cells isolated from WT mice, either non stimulated or at 5 different time points of stimulation with anti-CD3 and anti-CD4 antibodies (30s; 120s; 300s; 600s)
2019-09-27 | PXD012826 | Pride
Project description:Dynamic changes in histone acetylation patterns are mediated by the activity of histone acetyltransfereases (HATs) and histone deacetylases (HDACs) and are key events in the epigenetic regulation of gene expression. The application of HDAC inhibitors revealed a variety of T cell functions controlled by reversible lysine acetylation and HDAC1, HDAC2, HDAC3, HDAC7 and HDAC9 have been implicated in regulating T cell development and function. Nevertheless, unique functions of individual HDAC members in T cells and specific T cell functions that are regulated by HDACs are still only poorly understood. We previously showed that T cell-specific loss of HDAC1 (using the Cd4Cre deleter strain) leads to enhanced allergic airway inflammation and increased Th2 cytokine production. Interestingly, late T cell development was not impaired in these mice. However, HDAC2 was up-regulated in the absence of HDAC1, thus we hypothesized compensatory pathways/function between these two closely related class I HDAC family members in T cells. To investigate redundant and non-redundant functions of HDAC1 and HDAC2, we generated mice with a conditional T cell-specific (using Cd4Cre) combined loss of HDAC1 and HDAC2. As part of our study, we determined and compared the transcriptome of peripheral wild-type and HDAC1/2-null CD4+ T cells. Since loss of HDAC1/HDAC2 during late T cell development led to the appearance of MHC class II-selected CD4+ helper T cells that expressed CD8 lineage genes such as Cd8a and Cd8b1, we also analyzed the transcriptome of HDAC1/2-null CD4+CD8+ T cells.
2014-03-30 | E-MTAB-2184 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells play an important role in the induction and maintenance of peripheral tolerance. Treg cells also suppress a variety of other immune responses, including anti-tumor and alloimmune responses. We have previously reported that tumor-activated Treg cells express granzyme B and that granzyme B is important for Treg cell-mediated suppression of anti-tumor immune responses (GSE13409). Here, we report that allogeneic mismatch also induces the expression of granzyme B. Granzyme B-deficient mice challenged with fully mismatched allogeneic P815 mastocytoma cells have markedly improved survival compared to WT and other granzyme- or perforin-deficient mice, suggesting an immunoregulatory role for granzyme B in this setting. Treg cells harvested from the tumor environment of P815-challenged mice express granzyme B. Treg cells also express granzyme B in vitro during mixed lymphocyte reactions and in vivo in a mouse model of graft-versus-host disease (GVHD). However, in contrast to findings from our previously published tumor model, granzyme B is not required for the suppression of effector T cell (Teff) proliferation in in vitro Treg suppression assays stimulated by either Concanavalin A or allogeneic antigen presenting cells. Additionally, in an ex vivo assay, sort-purified in vivo-activated CD4+Foxp3+ Treg cells from mice with active GVHD -- under conditions known to induce granzyme B expression in Treg cells -- suppressed Teff cell proliferation in a granzyme B-independent manner. Adoptive transfer of naive granzyme B-deficient CD4+CD25+ Treg cells into a mouse model of GVHD rescued hosts from lethatlity equivalently to naive wild-type Treg cells. Serum analysis of GVHD-associated cytokine production in these recipients also demonstrated that Treg cells suppressed production of IL-2, IL-4, IL-5, GM-CSF, and IFN-gamma in a granzyme B-independent manner. In order to determine whether the context in which Treg cells are activated alters the intrinsic properties of Treg cells, we used Foxp3 reporter mice to obtain gene expression profiles of CD4+Foxp3+ Treg cells purifed from naive resting spleens, spleens from mice with acute GVHD, and from ascites fluid of mice challenged intraperitoneally with allogeneic P815 tumor cells. Unsupervised analyses revealed distinct activation signatures of Treg cells among the 3 experimental groups. Taken together, these findings demonstrate that granzyme B is not required for Treg cell-mediated suppression of GVHD, which is in contrast to what we have previously reported for Treg cell function in the setting of tumor challenge. Cell intrinsic differences could partially account for these differential phenotypes. These data also suggest the therapeutic potential of targeting specific Treg cell suppressive functions in order to segregate GVHD and graft-versus-tumor effector functions. Experiment Overall Design: Six replicates of Naive CD4+Foxp3+ Treg cells were purified from resting spleens, five replicates of allogeneic tumor-activated Treg cells and three samples of GVHD-activated Treg cells. Experiment Overall Design: Naive reps 1-3 are controls for the GVHD-activated samples. Experiment Overall Design: Naive reps 4-6 are controls for the Allogeneic tumor-activated samples.
2009-09-15 | E-GEOD-16210 | biostudies-arrayexpress