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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.
摘要：
Birdshot脉络膜视网膜病是一种与MHC-I等位基因HLA-A29密切相关的炎症性眼部疾病。与MHC-I的惊人关联表明T细胞参与，而自然杀伤（NK）细胞的参与仍未被研究。在这里，我们表明，HLA-A29阳性鸟脉络膜视网膜病变患者的NK细胞池偏斜，其中含有扩增的CD16阳性NK细胞，可产生更多的促炎细胞因子。这些NK细胞含有表达CD8A的群体，CD8A参与靶细胞的MHC-I识别，显示表明高细胞毒性活性的基因特征(GZMB，PRF1和ISG15），和通过NK细胞受体CD244（SH2D1B）的信号传导。对一群患有活动性疾病的鸟脉络膜视网膜病变患者的长期监测确定了CD8brightCD244brightNK细胞的群体，在成功治疗后临床缓解后迅速下降至正常水平。总的来说，这些研究提示CD8brightCD244brightNK细胞在鸟脉络膜视网膜病变中的作用。
