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Brain disorders

Attraction signals

Nature Reviews Neuroscience volume 24, page 131 (2023)Cite this article

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Radiation-induced brain injury (RIBI) is a common complication of brain radiation therapy, but its underlying mechanisms are poorly understood. Here, single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing of necrotic temporal lobe tissue from patients with RIBI showed that peripherally circulating CD8+ T cells infiltrate and clonally expand in the lesion site. To investigate the chemotactic cues that drive recruitment of these T cells, the authors used ligand–receptor pair scanning of the scRNA-seq data and other analyses to show that the chemokine ligands CCL2 and CCL8 and their interaction partners CCR2 and CCR5 were upregulated in lesion-associated pro-inflammatory microglial subtypes and infiltrating CD8+ T cells, respectively. Conditional knockout of Ccl2 and Ccl8 selectively in microglia in a mouse model of RIBI resulted in a reduction in infiltration of CD8+ T cells and a smaller lesion volume compared with wild-type mice; similar results were obtained following co-treatment with CCL2- and CCL8-neutralizing antibodies or administration of a dual antagonist against CCR2 and CCR5. Interestingly, microglia expressing CCL2 and CCL8 were also found to mediate CD8+ T cell infiltration in a mouse model of ischaemia. Overall, this study reveals a key chemotactic axis that mediates recruitment of T cells from the periphery following brain injury.

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  1. Nature Reviews Neuroscience http://www.nature.com/nrn/

    Sian Lewis

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  1. Sian Lewis
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Correspondence to Sian Lewis.

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Lewis, S. Attraction signals. Nat Rev Neurosci 24, 131 (2023). https://doi.org/10.1038/s41583-023-00678-w

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  • DOI: https://doi.org/10.1038/s41583-023-00678-w

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