A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model.
Nat Neurosci
; 26(10): 1713-1725, 2023 10.
Article
en En
| MEDLINE
| ID: mdl-37709997
ABSTRACT
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 adhesion molecule α4-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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Encefalomielitis Autoinmune Experimental
/
Esclerosis Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania