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Next generation sequencing compares CNS-infiltrating CD4 cells versus draining lymph node effector CD4 cells in experimental autoimmune encephalomyelitis

ABSTRACT: The immunology has been advanced mostly by studying peripheral blood in human and peripheral immune organ in mouse. However, a long standing problem in develop therapeutics treating autoimmune diseases is that we are short of knowledge about inflammatory-tissue infiltraing CD4 cells, which are terminally differentiated effector that exactly mediate the tissue damage. Thus, to address this issue, we induced experimental autoimmune encephalomyelitis (EAE) in mouse and sorted out both CNS infiltrating CD4 cells and draining lymph node effector CD4 cells at disease onset, and compared their transcriptome

ORGANISM(S): Mus musculus

PROVIDER: GSE192878 | GEO | 2022/01/04

REPOSITORIES: GEO

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Next generation sequencing compares CNS-infiltrating CD4 cells versus draining lymph node effector CD4 cells in experimental autoimmune encephalomyelitis

Project description:Next generation sequencing compares CNS-infiltrating CD4 cells versus draining lymph node effector CD4 cells in experimental autoimmune encephalomyelitis

| PRJNA793585 | ENA

Quantitative proteome profiling of CNS-infiltrating autoreactive CD4+ cells reveals selective changes during experimental autoimmune encephalomyelitis

Project description:Experimental autoimmune encephalomyelitis (EAE) is a murine model of multiple sclerosis, a chronic neurodegenerative and inflammatory autoimmune condition of the central nervous system (CNS). Pathology is driven by the infiltration of autoreactive CD4+ lymphocytes into the CNS where they attack neuronal sheaths causing ascending paralysis. We used an isotope-coded protein labelling approach to investigate the proteome of CD4+ cells isolated from the spinal cord and brain of mice at various stages of EAE progression in two EAE disease models; PLP139-151-induced relapsing-remitting EAE and MOG35-55-induced chronic EAE, which emulate the two forms of human multiple sclerosis. A total of 1120 proteins were quantified across disease onset, peak-disease and remission phases of disease and of these, 13 up-regulated proteins of interest were identified with functions relating to the regulation of inflammation, leukocyte adhesion and migration, tissue repair and the regulation of transcription/translation. Proteins implicated in processes such as inflammation (S100A4 and S100A9) and tissue repair (Annexin A1), which represent key events during EAE progression were validated by quantitative PCR. This is the first targeted analysis of autoreactive cells purified from the CNS during EAE, highlighting fundamental CD4+ cell-driven processes that occur during the initiation of relapse and remission stages of disease.

2016-07-08 | PXD001011 | Pride

The lysine acetyltransferase KAT6A epigenetically facilitates glucose metabolic programming and CD4+ T-cell responses in autoimmunity

Project description:Epigenetic programs are pivotal regulators of effector CD4+ T cells and determine the fate of many autoimmune disorders. Here, we show that the acetyltransferase KAT6A acts as a novel regulator of glucose metabolism that is required for the proliferation and effector functions of CD4+ T cells in autoimmunity. Clinical analysis shows that KAT6A in CD4+ T cells is linked to the progression of autoimmune Sjogren’s syndrome (SS) . Conditional knockout of KAT6A inhibits the proliferation and Th1/Th17 effector functions of CD4+ T cells both in vitro and that KAT6A-cKO CD4+T cells are less susceptible to induce adjuvant-immunized experimental autoimmune encephalomyelitis (EAE), autoimmune colitis and experimental SS. Combination of metabolomic, epigenetic and transcriptomic analyses show that KAT6A maintains abundant acetylation of H3K9ac and H3K27ac sites of several glycolytic genes, which in turn disrupts the transcriptional activation of MYC and HIF-1α, and potentiates the metabolic programming of glycolysis through its enzymatic amino acid points. Treatment with KAT6A small-molecule inhibitors in various autoimmune mice models shows high therapeutic value for targeting KAT6A to the treatment of autoimmune disorders. Our study reveals a critical role for KAT6A in autoimmunity via the epigenetic modification of glucose metabolic reprogramming and the effector response of CD4+ T cells.

2023-12-09 | GSE241099 | GEO

Gene expression analysis of CD4+ and CD4- ILC1 subsets by RNAseq

Project description:Innate lymphoid cell (ILC) subsets that mirror helper T cells in their effector cytokine profiles have recently emerged as central players in both homeostatic and inflammatory conditions. Like their Th1, Th2 and Th17/Th22 helper T cell counterparts, ILC subsets are categorized based on their expression of specific transcription factors and effector cytokines: group 1 ILC (ILC1) express T-bet and IFN-Î³; group 2 ILC (ILC2) express GATA-3 and type 2 effector cytokines such as IL-13 and IL-5; and group 3 ILC (ILC3) express RORgt and the cytokines IL-22 and/or IL-17. Under this nomenclature, natural killer (NK) cells and lymphoid tissue inducers (LTi) are considered ILC1 and ILC3, respectively. ILC1 contain both CD4+ and CD4- populations, but whether this phenotypic characteristic reflects functional differences between these two populations is unknown. These studies examine the gene expression profiles of CD4+ vs CD4- ILC1 in a cohort of healthy control subjects. ILC subsets were isolated from the peripheral blood of healthy control subjects. cDNA was isolated and amplified from sorted populations, and gene expression was analyzed by RNAseq

2015-12-31 | E-GEOD-69596 | biostudies-arrayexpress

Transcriptome of myelin oligodendrocyte glycoprotein (MOG)-reactive CD4 T cells and control CD4 T cells from draining lymp nodes and spleens of mice during experimental autoimmune encephalomyelitis (EAE)

Project description:MOG-reactive CD4 T cells were isolated from draining lymph nodes (dLN) and spleen of C57BL6/N female mice on day 10 after subcutaneous immunization with MOG(35-55) emulsified in Complete Freund’s adjuvant (CFA). Some mice received the CpG-B-1826 (50 microg; TCCATgACgTTCCTgACgTT; TIB MOLBIOL Syntheselabor GmbH), which was added to the MOG(35-55)/CFA mixture before emulsification. To isolate MOG-reactive CD4 T cells, dLN and spleens were harvested from mice on day 10 post-immunization, and single cell suspensions were re-stimulated for 5 hours using a mixture of MOG(35-55) (20 microg/ml), anti-CD40, anti-CD28, and anti-CD40L-PE (all from a commercial kit – Miltenyi Biotec – cat number 130-093-129). After 5 hours, CD4-positive cells were enriched magnetically by MACS using anti-CD4 microbeads (Miltenyi Biotec GmbH, cat. 130-049-201, clone L3T4), and subsequently subjected to FACS sorting to isolate CD4+CD40L+ and CD4+CD40L- cells after staining with anti-CD4 (clone RM4-5, conjugated to Pacific Blue), including a bin channel for CD8-positive cells (clone 53-6.7) and a marker for staining dead cells (NHPO). Sorted CD4+CD40L+ and CD4+CD40L- cells were then quickly checked for purity and directly lysed in 350 microlitre RLT buffer containing 1% beta-mercaptoethanol (Invitrogen). Purity was >95%. Mice were 6-10 weeks of age at the time of immunization. The goal was to identify genes differentially expressed between MOG-reactive CD4 T cells in mice treated or not with CpG-B, and to characterize the transcriptome of autoreactive CD4 T cells in draining lymph nodes and spleen on day 10 after immunization.

2023-04-26 | GSE205600 | GEO

Heterozygous Missense Mutation in the Coiled-Coil Domain of STAT5B

Project description:<p>We describe one patient with a heterozygous missense mutation in the coiled-coil domain of STAT5B. This patient presented with leukocytosis, lymphadenopathy, splenomegaly, necrotizing granulomas, hyper-IgM and autoimmune thrombocytopenia. Mutant STAT5B protein was shown to dominantly-interfere with IL2-induced transcriptional activity resulting in global downregulation of STAT5-regulated genes in patient T cells. The patient exhibited an increase in CD4+ T effector memory cells in the peripheral blood and these cells were resistant to restimulation-induced cell death <i>in vitro</i>. </p>

| phs001479 | dbGaP

equine CD4+ T cells show changed membrane protein expression in autoimmune uveitis

Project description:Through this comparative proteomic study of equine CD4+ cells 376 membrane proteins could be identified. Several proteins showed changed abundance in horses affected by a spontaneous autoimmune disease (equine recurrent uveitis, ERU). Findings provide novel knowledge about changes in the CD4+ immune cell membrane proteome in a spontaneously and naturally occurring autoimmune disease in horses. The data is highly relevant for veterinary medicine and has proven translational quality for autoimmune uveitis in man.

2017-01-09 | PXD005384 | Pride

Expression data of peripheral CD4+ T cells from young(6-8-week-old) and old(11-month-old) mice

Project description:We conducted gene expression profile analysis by using peripheral CD4+ T cells from young and old mice.Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the most prominent biological processes altered in peripheral CD4+ T cells from young and old mice were associated with cytoplasmic DNA-sensing, AKT signaling and autoimmune disease.

2023-06-01 | GSE153462 | GEO

Transcription profiling of human CD4 positive T cell subsets

Project description:Peripheral Blood Mononuclear Cells (PBMCs) were isolated from a buffy coat (Australian Blood Bank) using Ficoll methodology. CD4+ T cells were isolated using Dynal Beads kit. Pure CD4+ T cells were then stained using a cocktail of monoclonal antobodies (mAbs), including: anti-CD4PE, CD45RO ECD, CD62L APC-Cy7, CD25 APC, CD127 Pacific Blue. After incubation, cells were washed twice in PBS/FCS (0.2%), and sorted into five different cell subsets: CD4+CD25+CD127low CD62L+CD45RO- (naive regulatory T cells), CD4+CD25+CD127low CD62L+/- CD45RO+ (activated regulatory T cells), CD4+CD25+CD127hi CD62L+/- CD45RO+ (memory T cells), CD4+CD25-CD127low CD62L+/- CD45RO+ (effector T cells) and CD4+CD25-CD127hi CD62L+ CD45RO- (naive T cells).

2011-02-10 | E-MEXP-2578 | biostudies-arrayexpress

Gene expressions of CD4+ T cells in each developmental stages

Project description:The development of T cells has been characterized as taking place over three stages: naïve (Tn), central memory (Tcm), and effector memory (Tem) cells. Recently, stem cell memory T cells (Tscm) were found to be the least-developed memory subset. We performed detailed analysis of the gene expression of human CD4+ T cells with clear distinction of the Tn, Tscm, Tcm, and Tem stages. We sorted Tn, Tscm, Tcm, and Tem CD4+ T cells from the peripheral blood of six healthy volunteers to see the differences of gene expression between each developmental stage.

2015-05-12 | E-GEOD-61697 | biostudies-arrayexpress

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