| Autor: |
Kendirli, Arek, de la Rosa, Clara, Lämmle, Katrin F., Eglseer, Klara, Bauer, Isabel J., Kavaka, Vladyslav, Winklmeier, Stephan, Zhuo, La, Wichmann, Christian, Gerdes, Lisa Ann, Kümpfel, Tania, Dornmair, Klaus, Beltrán, Eduardo, Kerschensteiner, Martin, Kawakami, Naoto |
| Zdroj: |
Nature Neuroscience; October 2023, Vol. 26 Issue: 10 p1713-1725, 13p |
| Abstrakt: |
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. |
| Databáze: |
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