A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model.
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BiBTeXMultiple sclerosis (MS) involves the infiltration of autoreactive T cells into the CNS, yet we lack a comprehensive understanding of the signaling pathways that regulate this process. Here, we conducted a genome-wide in vivo CRISPR screen in a rat MS model and identified 5 essential brakes and 18 essential facilitators of T cell migration to the CNS. While the transcription factor ETS1 limits entry to the CNS by controlling T cell responsiveness, three functional modules, centered around the adhesion molecule alpha4-integrin, the chemokine receptor CXCR3 and the GRK2 kinase, are required for CNS migration of autoreactive CD4(+) T cells. Single-cell analysis of T cells from individuals with MS confirmed that the expression of these essential regulators correlates with the propensity of CD4(+) T cells to reach the CNS. Our data thus reveal key regulators of the fundamental step in the induction of MS lesions.
SEEK ID: http://lmmeisd-2.srv.mwn.de/publications/5
PubMed ID: 37709997
Projects: Published Datasets
Publication type: Journal
Journal: Nat Neurosci
Citation: Nat Neurosci. 2023 Oct;26(10):1713-1725. doi: 10.1038/s41593-023-01432-2. Epub 2023 Sep 14.
Date Published: 4th Oct 2023
Registered Mode: by PubMed ID
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Created: 28th Jun 2024 at 08:42
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Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
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Multiple sclerosis (MS) involves the infiltration of autoreactive T cells into the CNS, yet we lack a comprehensive understanding of the signaling pathways that regulate this process. Here, we conducted a genome-wide in vivo CRISPR screen in a rat MS model and identified 5 essential brakes and 18 essential facilitators of T cell migration to the CNS. While the transcription factor ETS1 limits entry to the CNS by controlling T cell responsiveness, three functional modules, centered around the ...
