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Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy

Author

Listed:
  • Pulak R. Nath

    (NIH
    A Miltenyi Biotec Company)

  • Mary Maclean

    (NIH
    NIAMS)

  • Vijay Nagarajan

    (NIH
    NIH)

  • Jung Wha Lee

    (NIH)

  • Mehmet Yakin

    (NIH)

  • Aman Kumar

    (NIH)

  • Hadi Nadali

    (NIH)

  • Brian Schmidt

    (NIH)

  • Koray D. Kaya

    (NIH)

  • Shilpa Kodati

    (NIH)

  • Alice Young

    (NIH)

  • Rachel R. Caspi

    (NIH)

  • Jonas J. W. Kuiper

    (University of Utrecht)

  • H. Nida Sen

    (NIH)

Abstract

Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines. These NK cells contain populations that express CD8A which is involved in MHC-I recognition on target cells, display gene signatures indicative of high cytotoxic activity (GZMB, PRF1 and ISG15), and signaling through NK cell receptor CD244 (SH2D1B). Long-term monitoring of a cohort of birdshot chorioretinopathy patients with active disease identifies a population of CD8bright CD244bright NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8bright CD244bright NK cells in birdshot chorioretinopathy.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50472-0
    DOI: 10.1038/s41467-024-50472-0
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    References listed on IDEAS

    as
    1. 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.
    2. Chao Yang & Jason R. Siebert & Robert Burns & Zachary J. Gerbec & Benedetta Bonacci & Amy Rymaszewski & Mary Rau & Matthew J. Riese & Sridhar Rao & Karen-Sue Carlson & John M. Routes & James W. Verbsk, 2019. "Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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