{Reference Type}: Journal Article
{Title}: Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.
{Author}: Nath PR;Maclean M;Nagarajan V;Lee JW;Yakin M;Kumar A;Nadali H;Schmidt B;Kaya KD;Kodati S;Young A;Caspi RR;Kuiper JJW;Sen HN;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Jul 31
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-50472-0
{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.