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.恒定自然杀伤T（invariant natural killer T, iNKT）细胞是一类异质性的终末分化、非循环的组织驻留T淋巴细胞，可识别CD1d分子提呈的糖脂类物质，包括α-半乳糖基神经酰胺（alpha-galactosylceramide, aGalCer）。本研究证实，小鼠与人类肝脏驻留的、结合α-半乳糖基神经酰胺/CD1d的iNKT细胞，属于一类新型的Zbtb16阳性、Tbx21阳性、Gata3阳性、Maf低表达、Rorc阴性的细胞亚群，该亚群具有显著的可塑性。这类细胞在反复接触经静脉递送的包被α-半乳糖基神经酰胺/CD1d的纳米颗粒（nanoparticles, NPs）后，会被诱导分化为免疫调节性、分泌IL-10与IL-21的高表达Maf细胞，这类细胞具备1型调节性T（T-regulatory type 1, TR1）样转录特征。