Rapid activation of IL-2 receptor signaling by CD301b+ DC-derived IL-2 dictates the outcome of helper T cell differentiation.
Rapid activation of IL-2 receptor signaling by CD301b+ DC-derived IL-2 dictates the outcome of helper T cell differentiation.
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CD301b DC 衍生的 IL-2 快速激活 IL-2 受体信号决定了辅助 T 细胞分化的结果。
DOI：
10.1101/2023.10.26.564276
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kumamoto,Yosuke
中科院分区：
文献类型：
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作者：
Tatsumi,Naoya;El-Fenej,Jihad;Davila-Pagan,Alejandro;Kumamoto,Yosuke
效应T辅助细胞（Th）分化是功能性适应性免疫的基础。树突状细胞（dc）的不同亚群优先诱导不同类型的Th细胞，但Th2型（Th2）分化的命运指令机制仍然是谜，因为关键的dc来源线索尚未明确确定。在这里，我们发现CD301b+ DC，一个主要的Th2诱导DC亚群，通过CD4T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，CD40参与诱导CD301b+ dc选择性地产生IL-2，以最大化CD25在CD4 T细胞中的表达，这是Th2命运决定所特别需要的。另一方面，CD301b+ dc中的CD25促进了IL-2对同源CD4T细胞的直接作用。此外，CD301b+ dc来源的IL-2使CD4T细胞偏离T滤泡辅助细胞的命运。这些结果突出了dc -内在CD40-IL-2轴在细胞命运分岔中的关键作用。
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.