A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model
2023-10 | journal article
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A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model
Kendirli, A.; de la Rosa, C.; Lämmle, K. F.; Eglseer, K.; Bauer, I. J.; Kavaka, V. & Winklmeier, S. et al. (2023)
Nature Neuroscience, 26(10) pp. 1713-1725. DOI: https://doi.org/10.1038/s41593-023-01432-2
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Details
- Authors
- 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
- 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.
- Issue Date
- October-2023
- Journal
- Nature Neuroscience
- Project
- TRR 274: Checkpoints of Central Nervous System Recovery
TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults - Working Group
- RG Kerschensteiner (Neuroimmune Interactions)
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- Language
- English