Tatsumi Naoya, El-Fenej Jihad, Davila-Pagan Alejandro, Kumamoto Yosuke
Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103.
Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103.
bioRxiv. 2023 Oct 31:2023.10.26.564276. doi: 10.1101/2023.10.26.564276.
Effector T helper (Th) cell differentiation is fundamental to functional adaptive immunity. Different subsets of dendritic cells (DCs) preferentially induce different types of Th cells, but the fate instruction mechanism for Th type 2 (Th2) differentiation remains enigmatic, as the critical DC-derived cue has not been clearly identified. Here, we show that CD301b DCs, a major Th2-inducing DC subset, drive Th2 differentiation through cognate interaction by 'kick-starting' IL-2 receptor signaling in CD4T cells. Mechanistically, CD40 engagement induces IL-2 production selectively from CD301b DCs to maximize CD25 expression in CD4 T cells, which is required specifically for the Th2 fate decision. On the other hand, CD25 in CD301b DCs facilitates directed action of IL-2 toward cognate CD4T cells. Furthermore, CD301b DC-derived IL-2 skews CD4T cells away from the T follicular helper fate. These results highlight the critical role of DC-intrinsic CD40-IL-2 axis in bifurcation of Th cell fate.
效应性辅助性T（Th）细胞分化是功能性适应性免疫的基础。不同亚群的树突状细胞（DC）优先诱导不同类型的Th细胞，但Th2细胞分化的命运决定机制仍然不明，因为关键的DC来源信号尚未明确鉴定。在此，我们表明，CD301b DC是诱导Th2的主要DC亚群，通过在CD4 T细胞中“启动”IL-2受体信号传导，通过同源相互作用驱动Th2分化。从机制上讲，CD40的结合选择性地诱导CD301b DC产生IL-2，以使CD4 T细胞中的CD25表达最大化，这是Th2命运决定所特需的。另一方面，CD301b DC中的CD25促进IL-2对同源CD4 T细胞的定向作用。此外，CD301b DC来源的IL-2使CD4 T细胞偏离滤泡辅助性T细胞命运。这些结果突出了DC内在的CD40-IL-2轴在Th细胞命运分叉中的关键作用。
