Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 5B17, 10 Center Dr, Bethesda, MD, 20892, USA.
Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Cell Mol Life Sci. 2023 Feb 27;80(3):76. doi: 10.1007/s00018-023-04726-7.
Invariant natural killer T (iNKT) cells correspond to a population of thymus-generated T cells with innate-like characteristics and effector functions. Among the various iNKT subsets, NKT17 is the only subset that produces the proinflammatory cytokine IL-17. But, how NKT17 cells acquire this ability and what would selectively trigger their activation remain incompletely understood. Here, we identified the cytokine receptor DR3 being specifically expressed on thymic NKT17 cells and mostly absent on other thymic iNKT subsets. Moreover, DR3 ligation promoted the in vivo activation of thymic NKT17 cells and provided costimulatory effects upon agonistic α-GalCer stimulation. Thus, we identified a specific surface marker for thymic NKT17 cells that triggers their activation and augments their effector functions both in vivo and in vitro. These findings provide new insights for deciphering the role and function of murine NKT17 cells and for understanding the development and activation mechanisms of iNKT cells in general.
不变自然杀伤 T(iNKT)细胞是一群具有先天样特征和效应功能的胸腺衍生 T 细胞。在各种 iNKT 亚群中，NKT17 是唯一产生促炎细胞因子 IL-17 的亚群。但是，NKT17 细胞如何获得这种能力，以及什么会选择性地触发它们的激活仍然不完全清楚。在这里，我们鉴定出细胞因子受体 DR3 特异性表达于胸腺 NKT17 细胞，而在其他胸腺 iNKT 亚群中则很少表达。此外，DR3 配体的交联促进了体内胸腺 NKT17 细胞的激活，并在激动性 α-GalCer 刺激下提供共刺激作用。因此，我们鉴定出一种用于胸腺 NKT17 细胞的特异性表面标记，它可以在体内和体外触发其激活并增强其效应功能。这些发现为解析小鼠 NKT17 细胞的作用和功能以及理解 iNKT 细胞的一般发育和激活机制提供了新的见解。
