Liver iNKT transcriptional profiling

Invariant NKT (iNKT) cells comprise a heterogeneous group of terminally differentiated, non-circulating, tissue-resident T-lymphocytes that recognize glycolipids, including alpha-galactosylceramide (aGalCer), in the context of CD1d. Here, we show that murine and human liver-resident aGalCer/CD1d-binding iNKTs correspond to a novel Zbtb16+/Tbx21+/Gata3+/Maflow/Rorc– subset that exhibits profound plasticity. Repetitive encounters of these cells with intravenously-delivered aGalCer/CD1d-coated nanoparticles (NPs) trigger their differentiation into immunoregulatory, IL-10/IL-21-producing, Mafhigh cells expressing a T-regulatory type 1 (TR1)-like transcriptional signature. Overall design: We defined the transcriptional profile of iNKT cells from liver of untreated NOD.c3c4, NOD and B6 mice. We compared the transcriptional profile of aGalCer/CD1d-NP-treated and untreated NOD.c3c4 mice. Finally, we also characterized the transcriptional profile of human liver iNKT cells.