Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196942 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Peptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
2014-07-14 | GSE46036 | GEO
Project description:Antigen-specific regulation of autoimmune disease is a major clinical research goal. In seropositive rheumatoid arthritis (RA), T cells help to autoreactive B cells matures the citrullinated antigen-specific immune response, generating RA-specific V-domain glycosylated anti-citrullinated (Cit) protein antibodies (VDG ACPA) before arthritis onset. Repeated low or escalating antigen doses administered under “sub-immunogenic” conditions generally favors tolerance. The aims of this study were to explore the safety, pharmacokinetics, immunological and clinical effects of s.c. DEN-181, comprising liposomes encapsulating self-peptide collagen II259-273 (CII) and NF-KB inhibitor 1,25-dihydroxycholecalciferol (calcitriol)
2022-12-05 | GSE208161 | GEO
Project description:Engineered cytokine-based approaches for immunotherapy of cancer are poised to enter the clinic, with IL-12 being at the forefront. However, little is known about potential mechanisms of resistance to cytokine therapies. We found that orthotopic murine lung tumors were resistant to systemically delivered IL-12 fused to murine serum albumin (MSA, IL12-MSA) due to low IL-12R expression on tumor-reactive CD8+ T cells. IL2-MSA increased binding of IL12-MSA by tumor-reactive CD8+ T cells, and combined administration of IL12-MSA and IL2-MSA led to enhanced tumor-reactive CD8+ T cell effector differentiation, decreased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells, and increased survival of lung tumor-bearing mice. Predictably, the combination of IL-2 and IL-12 at therapeutic doses led to significant dose-limiting toxicity. Administering IL-12 and IL-2 analogs with preferential binding to cells expressing IL12rb1 and CD25, respectively, led to a significant extension of survival in mice with lung tumors while abrogating dose-limiting toxicity. These findings suggest that IL-12 and IL-2 represent a rational approach to combination cytokine therapy whose dose-limiting toxicity can be overcome with engineered cytokine variants.
2024-01-26 | PXD044740 | Pride
Project description:Type I interferons (IFN-Is) are immunoregulatory cytokines that are essential for normal host antiviral responses. The current understanding is that IFN-Is mediate their effects through the expression of several hundred interferon-regulated genes. Here we identified a novel IFN-I response mechanism that relies on widespread changes in protein phosphorylation. IFN-I-induced phosphorylation in primary murine microglia and astrocytes – key IFN-I-responding cells of the central nervous system – was rapid and thus largely independent of gene expression. Based on in silico analysis, this mechanism relies predominantly on a small number of kinase families. Further, functional analysis suggested that this rapid response induces an immediate reactive state in cells and prepares them for the subsequent transcriptomic response. Similar extensive phosphoproteome changes were also present in a mouse model for IFN-I-induced neuroinflammatory diseases. Strikingly, the altered phosphoproteome in these transgenic mice predicted the clinical and pathological outcome of neuroinflammatory disease. These findings demonstrate for the first time a novel mechanism by which IFN-Is mediate cellular responses.
2021-11-02 | PXD014443 | Pride
Project description:This experiment compares the transciptional changes in antigen specific murine CD8 T cells (P14 T cells) after exposure in vivo to dendritic cells (DC) pulsed with low dose cognate peptide (1uM KAVYNFATC), high dose cognate peptide (100uM KAVYNFATC) or no antigen. Splenic dendritic cells were freshly isolated, peptide pulsed, washed and then adoptively transferred s.c. to the right footpad of C57BL/6 hosts. After 18h, freshly isolated P14 CD8 T cells were labelled with CMFDA and adoptively transferred iv. Two hours after T cell transfer, anti-L selectin antibody was given iv. At 12 and 24 hours, recipients were sacrificed and The right popliteal LN was harvested at 12 or 24h post T cell transfer and a single cell suspension was created and stained with PE CD4, B220 and CD19 (dump channel). Cells were then sorted on a FacsARIA for being non-doublets, CMFDA positive and dump channel negative. This experiment compares the transciptional changes in antigen specific murine CD8 T cells (P14 T cells) after exposure in vivo to dendritic cells (DC) pulsed with low dose cognate peptide (1uM KAVYNFATC), high dose cognate peptide (100uM KAVYNFATC) or no antigen. Splenic dendritic cells were freshly isolated, peptide pulsed, washed and then adoptively transferred s.c. to the right footpad of C57BL/6 hosts. After 18h, freshly isolated P14 CD8 T cells were labelled with CMFDA and adoptively transferred iv. Two hours after T cell transfer, anti-L selectin antibody was given iv. At 12 and 24 hours, recipients were sacrificed and The right popliteal LN was harvested at 12 or 24h post T cell transfer and a single cell suspension was created and stained with PE CD4, B220 and CD19 (dump channel). Cells were then sorted on a FacsARIA for being non-doublets, CMFDA positive and dump channel negative. The experiment was conducted for 39 samples out of which 35 passsed transcriptional quality control tests. The phenotypic distribution for the 35 samples includes: (1) high dose (100uM KAVYNFATC ) cognate peptide pulsed samples harvested at 12h post T cell transfer: 6 biological replicates (2) high dose (100uM KAVYNFATC ) cognate peptide pulsed samples harvested at 24h post T cell transfer: 7 biological replicates (3) low dose (1uM KAVYNFATC) cognate peptide pulsed samples harvested at 12h post T cell transfer: 6 biological replicates (4) low dose (1uM KAVYNFATC) cognate peptide pulsed samples harvested at 24h post T cell transfer: 9 biological replicates (5) no antigen pulsed samples harvested at 12h post T cell transfer: 3 biological replicates (6) no antigen pulsed samples harvested at 24h post T cell transfer: 4 biological replicates.
2013-11-21 | E-GEOD-49274 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF), a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles revealed a novel pathophysiologic function of myofibroblasts as a generator of reactive oxygen species, and a self-defense mechanism against oxidative stress of their own generating. Experiment Overall Design: We isolated two myofibroblast cell culture from patients with idiopathic pulmonary fibrosis. Embryonic pulmonary fibroblast was used for the reference.
2008-06-15 | E-GEOD-6804 | biostudies-arrayexpress
Project description:To further characterize the self-reactive T cell population and determine if there are sub-compartments within the naïve T cell pool that are more likely to respond in the absence of Treg cell-mediated control, we focused on CD5. CD5 is a membrane protein that is associated with the TCR and its expression is correlated with higher signaling intensity, presumably due to higher TCR self-MHC/peptide affinity, during positive selection. FACS was used to purify three distinct populations of naïve CD4+ T cells from the bottom, middle and top 10 percent based on CD5 expression; CD5low, CD5int and CD5high.
2015-08-04 | GSE70154 | GEO
Project description:Transcriptome in naturally-occuring self-reactive thymocytes
| PRJNA1172123 | ENA