Clinical and Translational Immunology Unit, Laboratory of Immunology, NEI, NIH, Bethesda, USA.
Lentigen Technology Inc., A Miltenyi Biotec Company, 910 Clopper Road, Gaithersburg, MD, 20878, USA.
Nat Commun. 2024 Jul 31;15(1):6443. doi: 10.1038/s41467-024-50472-0.
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 CD244 NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8 CD244 NK cells in birdshot chorioretinopathy.
鸟枪弹样脉络膜视网膜病变是一种与 MHC-I 等位基因 HLA-A29 强烈相关的炎症性眼病。与 MHC-I 的显著关联表明 T 细胞的参与，而自然杀伤 (NK) 细胞的参与在很大程度上仍未得到研究。在这里，我们表明 HLA-A29 阳性的鸟枪弹样脉络膜视网膜病变患者具有偏向性的 NK 细胞池，其中包含扩增的 CD16 阳性 NK 细胞，这些细胞产生更多的促炎细胞因子。这些 NK 细胞包含表达 CD8A 的群体，CD8A 参与靶细胞上的 MHC-I 识别，显示出高细胞毒性活性的基因特征（GZMB、PRF1 和 ISG15），并通过 NK 细胞受体 CD244（SH2D1B）信号传导。对一组患有活动性疾病的鸟枪弹样脉络膜视网膜病变患者进行的长期监测确定了一群 CD8 CD244 NK 细胞，在成功治疗后临床缓解时，这些细胞迅速降至正常水平。总之，这些研究表明 CD8 CD244 NK 细胞参与了鸟枪弹样脉络膜视网膜病变。
