Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset‐specific DC‐targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset‐specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF‐α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC‐based vaccination and therapy approaches.

中文翻译：

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内源性和外源性TLR3刺激后，小鼠肠道树突状细胞亚群的迁移。

淋巴结中对颗粒抗原的适应性免疫的启动很大程度上取决于迁移性树突状细胞（DC）的呈递。DC子集诱导特定类型免疫的能力各不相同，从而允许特定于子集的DC靶向影响疫苗接种和治疗效果。但是，忠实的药物设计需要对子集特异性与全局激活机制有确切的了解。cDC1是DC的子集，在支持针对病毒，细胞内细菌和肿瘤的免疫方面表现出色，它独特地表达了高水平的模式识别受体TLR3。使用各种鼠类遗传模型，我们在这里显示cDCs的cDC1和cDC2子集均被激活，并以细胞外源性和TNF-α依赖性方式同样良好地迁移，响应TLR3刺激，但是cDC1显示出对I型干扰素信号传导的独特要求。我们的发现揭示了调节DC子集迁移的常见和不同途径，为基于DC的疫苗接种和治疗方法的设计提供了重要的见识。