期刊
KIDNEY INTERNATIONAL
卷 99, 期 5, 页码 1140-1148出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2020.12.014
关键词
BK polyomavirus; BK polyomavirus?associated nephropathy; HLA-F; KIR3DS1; natural killer cells
资金
- program area ''Innovative Antiviral Therapies of the Heinrich Pette Institute
- Deutsches Zentrum fur Infektionsforschung
A recent study found that the activating natural killer cell receptor KIR3DS1 plays a protective role in controlling BK polyomavirus infection in the kidney, by regulating the interaction between HLA-F and KIR3DS1 to control disease progression, providing a rationale for exploring immunotherapeutic approaches for BK polyomavirus-associated nephropathy.
BK polyomavirus-associated nephropathy is a common complication after kidney transplantation leading to reduced graft function or loss. The molecular pathogenesis of BK polyomavirus-induced nephropathy is not well understood. A recent study had described a protective effect of the activating natural killer cell receptor KIR3DS1 in BK polyomavirus-associated nephropathy, suggesting a role of NK cells in modulating disease progression. Using an in vitro cell culture model of human BK polyomavirus infection and kidney biopsy samples from patients with BK polyomavirus-associated nephropathy, we observed significantly increased surface expression of the ligand for KIR3DS1, HLA-F, on BK polyomavirus-infected kidney tubular cells. Upregulation of HLA-F expression resulted in significantly increased binding of KIR3DS1 to BK polyomavirus-infected cells and activation of primary KIR3DS-positive natural killer cells. Thus, our data provide a mechanism by which KIR3DS-positive natural killer cells can control BK polyomavirus infection of the kidney, and rationale for exploring HLA-F/KIR3DS1 interactions for immunotherapeutic approaches in BK polyomavirusassociated nephropathy.
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