biostudies-literatureNath PRIntramural NIH HHS6443https://www.ebi.ac.uk/biostudies/studies/S-EPMC11291632biostudies-literatureUnknown15(1)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 populationNature communicationsSingle-cell profiling identifies a CD8^bright CD244^bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.PMC11291632ZIA EY000556Young ANath PRSchmidt BSen HNLee JWYakin MCaspi RRNadali HKaya KDKodati SMaclean MKuiper JJWNagarajan VKumar AfalseSingle-cell profiling identifies a CD8^bright CD244^bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.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 population2024-01-01T00:00:00Z2024 Jul2025-04-26T03:07:46.113Z2025-04-06T10:40:58.305ZS-EPMC112916323908519910.1038/s41467-024-50472-0