Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity
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Multidimensional single cell-analyses of T cells have fueled the debate about either extensive plasticity or “mixed” priming of T helper cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of T helper cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model of multiple sclerosis are distinct. i-T cells were Cxcr6+ and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter while i-T cells were also recruited to grey matter. Therefore, we propose that the definition of T helper cell subsets by their site of priming might guide an advanced understanding of T helper cell biology in health and disease.
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Created: 28th Jun 2024 at 08:49
Last updated: 10th Oct 2024 at 13:44
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Institutions: LMU Klinikum
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Institutions: LMU Klinikum
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Public web page: Not specified
Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa, Danio rerio
Submitter: Rainer Malik
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Assays: Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human) + smallRNA-seq (human), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (rat), Expression profiling: MERFISH Spatial Transcriptomics (mouse), Expression profiling: Microarray (zebrafish), Expression profiling: RiboTag-mRNA-seq (mouse), Expression profiling: Small RNA-seq (human), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics correlated Electron Micros..., Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human) (Day 20), Expression profiling: scRNA-seq (human) (Day 5), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse) + Bulk RNA-seq (mouse), Expression profiling: small RNA-seq (human), Expression profiling: small RNA-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: CUT&Tag sequencing (mouse), Genome binding/occupancy profiling: snATAC-seq (mouse), Genome wide (GW) and validation CRISPR screens (rat)
Snapshots: No snapshots
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Organisms: Mus musculus
SOPs: No SOPs
Data files: Tracking of CD4+ T cells during CNS autoimmunity
Snapshots: No snapshots
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Organisms: Mus musculus
SOPs: No SOPs
Data files: Skin and gut imprinted T helper cell subsets ex...
Snapshots: No snapshots
Submitter: Aditi Methi
Assay type: Epigenomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Organisms: Mus musculus
SOPs: No SOPs
Data files: Skin and gut imprinted T helper cell subsets ex...
Snapshots: No snapshots
Comparison of DNA accessibility by Omni-ATAC-seq in sorted effector i- and m-T cells (mD2RED CD4+ CD44high) and naive i- and m-T cells (mD2RED CD4+ CD44int) from spleen
Creators: None
Submitter: Aditi Methi
Investigations: Transcriptomics (Published)
We sorted i- and m-T cells (mD2REDCD4+CD44high) from lymph nodes and spleens of 2D2 x TH PhamT mice and performed RNAseq
Creators: None
Submitter: Rainer Malik
Investigations: Transcriptomics (Published)
Here, we use in vivo labeling at defined anatomical sites for "provance" tracking of immune cells across compartmental borders in the context of experimental autoimmune encephalomyelitis (EAE). Specifically, we labeled T cells in mesenteric or inguinal lymph nodes (LNs) of T cell conditional mitoDendra2 reporter mice via photoconversion at disease onset and re-isolated photoconverted T cells form the LNs, spleen and CNS two days later and we performed scRNA-seq on them. Our experimental system ...
Creators: None
Submitter: Rainer Malik
Investigations: Transcriptomics (Published)
Single-cell transcriptome profiling of disease-related lymphocytes in patients with multiple sclerosis
Creators: None
Submitter: Rainer Malik
Investigations: Transcriptomics (Published)
Abstract (Expand)
Authors: M. Hiltensperger, E. Beltran, R. Kant, S. Tyystjarvi, G. Lepennetier, H. Dominguez Moreno, I. J. Bauer, S. Grassmann, S. Jarosch, K. Schober, V. R. Buchholz, S. Kenet, C. Gasperi, R. Ollinger, R. Rad, A. Muschaweckh, C. Sie, L. Aly, B. Knier, G. Garg, A. M. Afzali, L. A. Gerdes, T. Kumpfel, S. Franzenburg, N. Kawakami, B. Hemmer, D. H. Busch, T. Misgeld, K. Dornmair, T. Korn
Date Published: 9th Jun 2021
Publication Type: Journal
PubMed ID: 34099917
Citation: Nat Immunol. 2021 Jul;22(7):880-892. doi: 10.1038/s41590-021-00948-8. Epub 2021 Jun 7.