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Targeting HDAC1 enzymatic activity in T cells protects against experimental autoimmune encephalomyelitis

ABSTRACT: Targeting HDAC1 enzymatic activity in T cells protects against experimental autoimmune encephalomyelitis

PROVIDER: PRJNA949156 | ENA |

REPOSITORIES: ENA

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Targeting HDAC1 enzymatic activity in T cells protects against experimental autoimmune encephalomyelitis

Project description:Histone deacetylases are key epigenetic regulators that control T cell-mediated immunity. A T cell-specific deletion of Hdac1 (HDAC1cKO) protects mice against experimental autoimmune encephalomyelitis (EAE). However, it remains elusive whether inhibition of HDAC1 enzymatic activity and thus mimicking HDAC1 inhibitor treatment is sufficient to block EAE induction. In order to address this question, we generated a novel mouse strain that expresses catalytically inactive HDAC1 (HDAC1Off) from the Rosa26 locus in HDAC1cKO CD4+ T cells to mimic selective inhibition of HDAC1 enzymatic activity in vivo. Mice expressing wildtype HDAC1 in HDAC1cKO CD4+ T cells (HDAC1On) were generated as corresponding controls. In contrast to HDAC1On mice, HDAC1Off mice did not develop EAE, and this correlated with diminished leukocyte CNS infiltration. HDAC1Off CD4+ T cells in the CNS displayed a severe reduction of IFNγ, IL-17A and TNFα proinflammatory cytokine expression. In vivo activated HDAC1Off CD4+ T cells downregulated gene sets associated with T cell activation, inflammatory response and cell migration, indicating impaired effector functions of HDAC1Off CD4+ T cells. Thus, our study demonstrates that the inhibition of the catalytic activity of HDAC1 is sufficient to achieve a clinical benefit in EAE disease development. This raises the exciting translational perspective that targeting HDAC1 enzymatic activity is a promising therapeutic strategy in treating human T cell-mediated autoimmune diseases.

2024-10-25 | GSE228259 | GEO

MAIT cells in experimental autoimmune encephalomyelitis (EAE)

Project description:MAIT cells in experimental autoimmune encephalomyelitis (EAE)

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Mouse brain proteome map of Experimental autoimmune encephalomyelitis (EAE) mouse model

Project description:Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, our aim was to build a proteome map of the biological changes that occur during MS at the major onset sites—the brain and the spinal cord. We performed quantitative proteome profiling in five specific brain regions and the spinal cord of EAE and healthy mice with high-resolution mass spectrometry based on tandem mass tags.

2019-02-25 | PXD011428 | Pride

Upregulation of PGC-1α in Neurons Protects Against Experimental Autoimmune Encephalomyelitis

Project description:Upregulation of PGC-1α in Neurons Protects Against Experimental Autoimmune Encephalomyelitis

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Transcriptomic profiling of choroid plexus in experimental autoimmune encephalomyelitis

Project description:Multiple sclerosis (MS) is a demyelinating disease causing major neurological disability in young adults. We characterized the transcriptome of the choroid plexus (CP), which is part of the blood-brain barriers and the major site of cerebrospinal fluid (CSF) production, in the experimental autoimmune encephalomyelitis mouse model of MS. Genes encoding for adhesion molecules, chemokines and cytokines displayed the most altered expression, supporting the CP as a site of immune-brain interaction in MS. The gene encoding for lipocalin 2 (LCN2) was the most up-regulated, and CSF LCN2 levels coincided with the phases of active disease. Total RNA was isolated with Trizol (Invitrogen, Carlsbad, CA, USA) following the manufacturer’s instructions. After quality assessment using the Agilent Bioanalyzer (Agilent Technologies, CA, USA), 100ng of total RNA from 3 pooled controls and 3 or 2 pooled samples of each experimental autoimmune encephalomyelitis (EAE) phase were amplified and labelled with the Illumina TotalPrep RNA Amplification Kit (Illumina Inc., San Diego, CA, USA). The labeled cRNA was then hybridized using the recommended protocol in a total of two Illumina Whole-Genome MouseRef-8 expression Beadchips (Illumina Inc., San Diego, CA, USA).

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Peli1 knock-out and wild type mouse brain proteomes during the disease course of experimental autoimmune encephalomyelitis

Project description:The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis since the knock-out induced less activated microglia and less inflammation in the CNS of experimental autoimmune encephalomyelitis in mice. In the present study the brain proteomes of Peli1 knock-out mice and wild-type mice were analyzed and compared before disease induction and after 10 and 20 days of experimental autoimmune encephalomyelitis using quantitative proteomics. The brain samples were analyzed using TMT labeling of small pools of samples and verified using label-free of individual mice.

2016-09-27 | PXD003710 | Pride

MAIT cells in experimental autoimmune encephalomyelitis (EAE)

Project description:Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS) most likely caused by autoreactive T cells. Mucosal-associated invariant T (MAIT) cells are characterized by a semi-invariant T cell receptor (TCR) with which they recognize 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a metabolite of the riboflavin (vitamin B2) pathway only present in yeast and bacteria. MAIT cells have been detected in inflamed brain lesions of MS patients. However, functional analyses of CNS-infiltrating MAIT cells are lacking and require a characterisation in the MS animal model experimental autoimmune encephalomyelitis (EAE).

2024-09-30 | GSE234291 | GEO

Differential expression of genes in spinal cord folowing experimental autoimmune encephalomyelitis (EAE) in mice.

Project description:Microarrays were used to identify genes that were differently expressed in mouse spinal cord as a resut of experimental autoimmune encephalomyelitis (EAE), which is a model for demyelinating disease. Mice were injected with PLP peptide or vechicle.

2013-08-01 | E-GEOD-44989 | biostudies-arrayexpress

Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis

Project description:Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis

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Differential expression of genes in spinal cord folowing experimental autoimmune encephalomyelitis (EAE) in mice.

2013-08-01 | GSE44989 | GEO