Dendritic cells (DCs) of the cDC2 lineage initiate allergic immunity and in the dermis are marked by their expression of CD301b. CD301b⁺ dermal DCs respond to allergens encountered in vivo, but not in vitro. This suggests that another cell in the dermis may sense allergens and relay that information to activate and induce the migration of CD301b⁺ DCs to the draining lymph node (dLN). Using a model of cutaneous allergen exposure, we show that allergens directly activated TRPV1⁺ sensory neurons leading to itch and pain behaviors. Allergen-activated sensory neurons released the neuropeptide Substance P, which stimulated proximally located CD301b⁺ DCs through the Mas-related G-protein coupled receptor member A1 (MRGPRA1). Substance P induced CD301b⁺ DC migration to the dLN where they initiated T helper-2 cell differentiation. Thus, sensory neurons act as primary sensors of allergens, linking exposure to activation of allergic-skewing DCs and the initiation of an allergic immune response.

cDC2 谱系的树突细胞 (DC) 启动过敏性免疫，并且在真皮中以表达 CD301b 为标志。CD301b ⁺真皮 DCs 对体内遇到的过敏原有反应，但在体外没有反应。这表明真皮中的另一个细胞可能感知过敏原并传递该信息以激活和诱导 CD301b ⁺ DC迁移到引流淋巴结 (dLN)。使用皮肤过敏原暴露模型，我们表明过敏原直接激活 TRPV1 ⁺感觉神经元，导致瘙痒和疼痛行为。过敏原激活的感觉神经元释放神经肽物质 P，刺激位于近端的 CD301b ⁺DCs 通过 Mas 相关 G 蛋白偶联受体成员 A1 (MRGPRA1)。物质 P 诱导 CD301b ⁺ DC 迁移到 dLN，在那里它们开始 T 辅助细胞 2 细胞分化。因此，感觉神经元充当过敏原的主要传感器，将暴露与过敏倾斜 DC 的激活和过敏免疫反应的启动联系起来。