Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has been associated with different forms of immune compromise. This study analyzes the chemokine signals and attracted immune cells in cerebrospinal fluid (CSF) during PML to define immune cell subpopulations relevant for the PML immune response. In addition to chemokines that indicate a general state of inflammation, like CCL5 and CXCL10, the CSF of PML patients specifically contains CCL2 and CCL4. Single-cell transcriptomics of CSF cells suggests an enrichment of distinct CD4+ and CD8+ T cells expressing chemokine receptors CCR2, CCR5, and CXCR3, in addition to ITGA4 and the genetic PML risk genes STXBP2 and LY9. This suggests that specific immune cell subpopulations migrate into the central nervous system to mitigate PML, and their absence might coincide with PML development. Monitoring them might hold clues for PML risk, and boosting their recruitment or function before therapeutic immune reconstitution might improve its risk-benefit ratio. [Display omitted] •Single-cell and proteomic analysis of cerebrospinal fluid in PML and controls•Specific increase of CCL2 and CCL4 in PML CSF•Enrichment of distinct T cell subclusters expressing CCR2, CCR5, and CXCR3 in PML CSF Deffner et al. analyze chemotactic signals and immune cell populations in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. This study reveals specific enrichment of chemokines and attracted T cell populations expressing the corresponding chemokine receptors, indicating their involvement in intrathecal anti-JCPyV immune response.