A CD8 + NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis
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Smilek, Dawn E.
Nature Publishing Group UK
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McKinney, E. F., Cuthbertson, I., Harris, K. M., Smilek, D. E., Connor, C., Manferrari, G., Carr, E. J., et al. (2021). A CD8 + NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis. Nature Communications, 12 (1)https://doi.org/10.1038/s41467-020-20594-2
Abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with the majority of cases characterised by relapsing/remitting (RRMS) attacks of neurologic dysfunction followed by variable resolution. Improving clinical outcomes in RRMS requires both a better understanding of the immunological mechanisms driving recurrent demyelination and better means of predicting future disease course to facilitate early targeted therapy. Here, we apply hypothesis-generating network transcriptomics to CD8+ cells isolated from patients in RRMS, identifying a signature reflecting expansion of a subset of CD8+ natural killer cells (NK8+) associated with favourable outcome. NK8+ are capable of regulating CD4+ T cell activation and proliferation in vitro, with reduced expression of HLA-G binding inhibitory receptors and consequent reduced sensitivity to HLA-G-mediated suppression. We identify surrogate markers of the NK8+ signature in peripheral blood leucocytes and validate their association with clinical outcome in an independent cohort, suggesting their measurement may facilitate early, targeted therapy in RRMS.
Article, /631/378/371, /692/617/375/1666, /45/91, /38, article
RCUK | Medical Research Council (MRC) (MR/L019027)
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) (UM1AI109565)
Wellcome Trust (Wellcome) (104064/Z/14/Z)
External DOI: https://doi.org/10.1038/s41467-020-20594-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316771
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/