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

Nat Commun. 2024 Jul 31;15(1):6443. doi: 10.1038/s41467-024-50472-0.

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.

MeSH terms

  • Adult
  • Birdshot Chorioretinopathy* / immunology
  • Birdshot Chorioretinopathy* / metabolism
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Chorioretinitis / genetics
  • Chorioretinitis / immunology
  • Cytokines / metabolism
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • HLA-A Antigens* / genetics
  • HLA-A Antigens* / immunology
  • HLA-A Antigens* / metabolism
  • Humans
  • Killer Cells, Natural* / immunology
  • Killer Cells, Natural* / metabolism
  • Male
  • Middle Aged
  • Perforin
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Signaling Lymphocytic Activation Molecule Family* / genetics
  • Signaling Lymphocytic Activation Molecule Family* / metabolism
  • Single-Cell Analysis* / methods

Substances

  • HLA-A29 antigen
  • HLA-A Antigens
  • Signaling Lymphocytic Activation Molecule Family
  • CD8 Antigens
  • CD244 protein, human
  • Receptors, IgG
  • PRF1 protein, human
  • Cytokines
  • CD8 antigen, alpha chain
  • GPI-Linked Proteins
  • FCGR3B protein, human
  • Perforin