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CSF CD4+ T cells in MS

ABSTRACT: CSF CD4+ T cells in MS

PROVIDER: PRJNA721683 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14230100_1.fastq.gz	Fastqsanger.gz
	SRR14230100_2.fastq.gz	Fastqsanger.gz
	SRR14230101_1.fastq.gz	Fastqsanger.gz
	SRR14230101_2.fastq.gz	Fastqsanger.gz
	SRR14230102_1.fastq.gz	Fastqsanger.gz

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scRNAseq of blood and CSF CD4+ T cells from MS patients and controls

Project description:To study the regulation of candidate genes from our study in human cells, we analyzed CD4+ T cells from blood and CSF of MA patients and age and sex matched idiopathic intracranial hypertension controls We analyzed 40845 cells in control blood, 807 cells in control CSF, 29749 cells in MS blood and 15768 cells in MS CSF

2023-08-01 | GSE232343 | GEO

scRNAseq of blood and CSF CD4+ T cells from MS patients and controls

Project description:scRNAseq of blood and CSF CD4+ T cells from MS patients and controls

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Single cell immune profiling reveals a developmentally distinct CD4+ GM-CSF+ T cell lineage that induces GI tract GVHD

Project description:Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft versus host disease (GVHD). CD4+ T cells that produce GM-CSF have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if there exists a unique CD4+ GM-CSF+ subset that differs from other defined T helper (TH) subtypes. Using single cell RNA sequencing analysis, we identified two CD4+ GM-CSF+ T cell populations that arose during GVHD and were distinguishable by the presence or absence of IFN-γ co-expression. CD4+ GM-CSF+ IFN-γ- T cells which emerged preferentially in the colon had a distinct transcriptional profile, employed unique gene regulatory networks, and possessed a non-overlapping TCR repertoire when compared to CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T cell populations in the colon. Functionally, this CD4+ GM-CSF+ T cell population contributed to pathological damage in the GI tract which was critically dependent upon signaling through the IL-7 receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic TH GM-CSF+ subset that mediates immunopathology.

2022-01-14 | GSE193475 | GEO

Transcriptional profiling of brain CD4+ and CD8+ TRM cells reveals dominant presence in white and grey matter in Multiple Sclerosis (MS)

Project description:The human brain is populated by perivascular CD8+ and CD4+ T cells with a tissue-resident memory T (TRM)-cell phenotype. In multiple sclerosis (MS), these cells associate with white matter (WM) and, to a lesser extent, grey matter (GM) lesions. We here investigated the transcriptional and functional profile of brain-resident T cells. Of n=11 subsequent post-mortem brain donors, we isolated CD8+ and CD4+ effector memory and effector memory re-expressing CD45RA T cells from blood and CD8+ and CD4+ CD69+ T cells from corpus callosum WM and cortical GM. Additionally, brain CD69+ T cells were sorted from subcortical WM, corpus callosum WM, and medulla WM/GM of n=3–5 brain donors as well as from paired normal-appearing WM and GM and from WM and GM lesions of n=6 MS brain donors. In all donors, WM and GM T cells were overwhelmingly CD69+CD103+/-. Bulk RNA sequencing of CD8+ and CD4+ CD69+ T cells revealed TRM-cell signatures, as marked by differential expression of, among others, SELL (CD62L), ITGA1 (CD49a), and S1PR1. Notably, gene expression hardly differed between lesional and normal-appearing WM CD8+ and CD4+ CD69+ T cells in MS brains. Genes up-regulated in brain TRM cells were MS4A1 (CD20) and SPP1 (osteopontin, OPN). OPN is also abundantly expressed by microglia and has been shown to inhibit T-cell activity. In line with the increased presence of OPN in active MS lesions, we noticed a reduced production of the inflammatory cytokines IL-2, TNF, and IFNγ by MS lesion-derived CD8+ and CD4+ T cells ex vivo. This study discloses essential characteristics of human brain CD8+ and CD4+ TRM cells in non-MS and MS post-mortem WM and GM, reports OPN as a generic product of brain-resident immune cells, and shows a tight control of the activation state of TRM cells in MS lesions.

2022-12-05 | GSE216028 | GEO

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2017-02-21 | E-MTAB-5412 | biostudies-arrayexpress

ATAC-seq of the following human primary CD4 T cell subsets: GM-CSF producing, GM-CSF negative, bulk, memory and naive CD4 T cells.

Project description:ATAC-seq of the following human primary CD4 T cell subsets: GM-CSF producing, GM-CSF negative, bulk, memory and naive CD4 T cells.

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mRNA-seq of the following human primary CD4 T cell subsets: GM-CSF producing, GM-CSF negative, bulk, memory and naive CD4 T cells.

Project description:mRNA-seq of the following human primary CD4 T cell subsets: GM-CSF producing, GM-CSF negative, bulk, memory and naive CD4 T cells.

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CSF CD4+ T cells in MS

Project description:Single-cell transcriptome profiling of disease-related lymphocytes in patients with multiple sclerosis

2021-04-14 | GSE172003 | GEO

The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells

Project description:Interleukin-21 (IL-21) has broad actions on T- and B-cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive M-NM-1-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive-transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon (IFN)-M-NM-3-producing CD4+ T cells in Il21r-/-Rag2-/- mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2-/- mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response. Total 6 samples were examined. Splenic dendritic cells were treated with IL-21 and/or GM-CSF studying STAT3 and STAT5B binding in the genome

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