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

Nath P. R., Maclean M., Nagarajan V., Lee J. W., YAKIN M., Kumar A., ...More

Nature Communications, vol.15, no.1, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 1
  • Publication Date: 2024
  • Doi Number: 10.1038/s41467-024-50472-0
  • Journal Name: Nature Communications
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Geobase, INSPEC, MEDLINE, Veterinary Science Database, Directory of Open Access Journals, Nature Index
  • Lokman Hekim University Affiliated: Yes

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.