Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy

Pulak R. Nath (), Mary Maclean, Vijay Nagarajan, Jung Wha Lee, Mehmet Yakin, Aman Kumar, Hadi Nadali, Brian Schmidt, Koray D. Kaya, Shilpa Kodati, Alice Young, Rachel R. Caspi, Jonas J. W. Kuiper () and H. Nida Sen
Additional contact information
Pulak R. Nath: NIH
Mary Maclean: NIH
Vijay Nagarajan: NIH
Jung Wha Lee: NIH
Mehmet Yakin: NIH
Aman Kumar: NIH
Hadi Nadali: NIH
Brian Schmidt: NIH
Koray D. Kaya: NIH
Shilpa Kodati: NIH
Alice Young: NIH
Rachel R. Caspi: NIH
Jonas J. W. Kuiper: University of Utrecht
H. Nida Sen: NIH

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50472-0

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