摘要：SummaryInvariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects ofin vivoiNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect onin vivoiNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic.Graphical abstractDisplay OmittedHighlights•NKTT320 rapidly activates iNKTin vivo, modulating downstream immune function•In vivoNKTT320 treatment modulates pro- and anti-inflammatory genes•NKTT320 treatment results in activation of innate and adaptive immune subsets•NKTT320 has promise as an immunotherapeutic with translational potentialBiological sciences; Immunology; Components of the immune system; Transcriptomics
