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- W4313404902 abstract "Abstract Natural Killer (NK) cells are innate antiviral and antitumor effector cells that have emerged as potent regulators of adaptive immune responses. However, NK cells are known to be dysfunctional in many diseases including systemic lupus erythematosus (lupus), where inability to restrain autoreactive T and B cells leads to potentially irreversible organ damage. To determine mechanisms driving NK-cell dysfunction in autoimmunity, we performed transcriptomic analysis of these cells in pediatric patients with lupus. Analysis of the differentially expressed genes revealed a putative gene regulatory node controlled by the heterodimeric pairing of the transcription factors EPAS1 and ARNT that is active in NK cells from patients with lupus, but not controls. Cytokines linked to lupus promote up-regulation of the protein encoded by EPAS1 in NK cells. Small molecule inhibitors of EPAS1 (PT2385) enhanced the capacity of NK cells to kill K562 cells. These results suggest that a hypoxia-related transcriptional program contributes to functional restraint of NK cells in lupus. Supported by T32GM063483, AR073228, AR47363 (Flow Cytometry Core), DK78392 (Flow Cytometry Core), DK90971 (Flow Cytometry Core)" @default.
- W4313404902 created "2023-01-06" @default.
- W4313404902 creator A5061193631 @default.
- W4313404902 date "2022-05-01" @default.
- W4313404902 modified "2023-10-16" @default.
- W4313404902 title "Hypoxia-inducible factor regulation of NK cell dysfunction in lupus" @default.
- W4313404902 doi "https://doi.org/10.4049/jimmunol.208.supp.55.06" @default.
- W4313404902 hasPublicationYear "2022" @default.
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