Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Immunity. 2020 Nov 17;53(5):1063-1077.e7. doi: 10.1016/j.immuni.2020.10.001. Epub 2020 Oct 23.
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.
树突状细胞 (DCs) 的 cDC2 谱系启动过敏免疫，在真皮中以其表达 CD301b 为标志。CD301b 真皮 DCs 对体内遇到的过敏原作出反应，但在体外则不会。这表明真皮中的另一种细胞可能会感知过敏原，并将信息传递给激活和诱导 CD301b DC 迁移到引流淋巴结 (dLN) 的细胞。我们使用皮肤过敏原暴露模型表明，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 P 物质，通过 Mas 相关 G 蛋白偶联受体成员 A1 (MRGPRA1) 刺激附近的 CD301b DCs。P 物质诱导 CD301b DC 迁移到 dLN，在那里它们启动辅助性 T 细胞 2 分化。因此，感觉神经元作为过敏原的主要传感器，将暴露与过敏偏倚 DC 的激活以及过敏免疫反应的启动联系起来。
