Single-cell profiling identifies a CD8 bright CD244 bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.

Autor: Nath PR; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA. hellopran2000@gmail.com.; Lentigen Technology Inc., A Miltenyi Biotec Company, 910 Clopper Road, Gaithersburg, MD, 20878, USA. hellopran2000@gmail.com., Maclean M; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA.; Translational Immunology Section, Office of Science and Technology, NIAMS, Bethesda, NIH, USA., Nagarajan V; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA.; Immunoregulation Section, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Lee JW; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Yakin M; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Kumar A; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Nadali H; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Schmidt B; NIH Intramural Sequencing Center, NIH, Rockville, USA., Kaya KD; Medical Genetics and Ophthalmic Genomics Unit, NEI, NIH, Bethesda, USA., Kodati S; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Young A; NIH Intramural Sequencing Center, NIH, Rockville, USA., Caspi RR; Immunoregulation Section, Laboratory of Immunology, NEI, NIH, Bethesda, USA., Kuiper JJW; Department of Ophthalmology, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands. j.j.w.kuiper@umcutrecht.nl., Sen HN; Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 31; Vol. 15 (1), pp. 6443. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1038/s41467-024-50472-0
Abstrakt: 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 CD8 bright CD244 bright NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8 bright CD244 bright NK cells in birdshot chorioretinopathy.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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