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A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis

Author

Listed:
  • Eoin F. McKinney

    (Jeffrey Cheah Biomedical Centre
    University of Cambridge School of Clinical Medicine)

  • Iona Cuthbertson

    (University of Cambridge School of Clinical Medicine)

  • Kristina M. Harris

    (ITN)

  • Dawn E. Smilek

    (ITN)

  • Christopher Connor

    (University of Cambridge School of Clinical Medicine)

  • Giulia Manferrari

    (University of Cambridge School of Clinical Medicine)

  • Edward J. Carr

    (University of Cambridge School of Clinical Medicine)

  • Scott S. Zamvil

    (University of California)

  • Kenneth G. C. Smith

    (Jeffrey Cheah Biomedical Centre
    University of Cambridge School of Clinical Medicine)

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.

Suggested Citation

  • Eoin F. McKinney & Iona Cuthbertson & Kristina M. Harris & Dawn E. Smilek & Christopher Connor & Giulia Manferrari & Edward J. Carr & Scott S. Zamvil & Kenneth G. C. Smith, 2021. "A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20594-2
    DOI: 10.1038/s41467-020-20594-2
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    Cited by:

    1. Pulak R. Nath & Mary Maclean & Vijay Nagarajan & Jung Wha Lee & Mehmet Yakin & Aman Kumar & Hadi Nadali & Brian Schmidt & Koray D. Kaya & Shilpa Kodati & Alice Young & Rachel R. Caspi & Jonas J. W. Ku, 2024. "Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Stefano Garofalo & Germana Cocozza & Alessandro Mormino & Giovanni Bernardini & Eleonora Russo & Donald Ielpo & Diego Andolina & Rossella Ventura & Katiuscia Martinello & Massimiliano Renzi & Sergio F, 2023. "Natural killer cells and innate lymphoid cells 1 tune anxiety-like behavior and memory in mice via interferon-γ and acetylcholine," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. James J. Gilchrist & Seiko Makino & Vivek Naranbhai & Piyush K. Sharma & Surya Koturan & Orion Tong & Chelsea A. Taylor & Robert A. Watson & Alba Verge los Aires & Rosalin Cooper & Evelyn Lau & Sara D, 2022. "Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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