Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12
Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12
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DOI：
10.1182/blood-2012-07-446054
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发表时间：
2013-04-11
期刊：
影响因子：
20.3
通讯作者：
Larregina, Adriana T.
中科院分区：
文献类型：
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作者：
Janelsins, Brian M.;Sumpter, Tina L.;Larregina, Adriana T.
P物质和血激肽-1是促炎性神经肽，通过与神经激肽-1受体(NK1R)激动性结合，具有促进1型免疫的潜能。树突状细胞(DC)是一种专职的抗原提呈细胞，启动和调节先天和获得性免疫反应的结果。在积极免疫技术的发展中，免疫刺激性树突状细胞受到高度重视。DC表达功能性的NK1R；然而，无论其潜在的DC刺激功能如何，NK1R激动剂促进免疫刺激DC的能力仍未被探索。在这里，我们证明，NK1R信号激活治疗性DC，能够通过抑制IL-10的合成和分泌而偏向1型免疫，而不影响其低水平的IL-12产生。在皮肤注射NK1R信号的DC后，观察到的有效的1型效应免疫反应需要它们归巢于皮肤引流淋巴结(SDLN)，在那里它们诱导炎症，并允许内源性-常规sDLN驻留和招募的炎症性DC分泌IL-12。我们的数据表明，NK1R信号促进免疫刺激性DC，并为神经介质用于调节先天性和获得性免疫反应的机制提供了相关的见解。
Substance-P and hemokinin-1 are proinflammatory neuropeptides with potential to promote type 1 immunity through agonistic binding to neurokinin-1 receptor (NK1R). Dendritic cells (DCs) are professional antigen-presenting cells that initiate and regulate the outcome of innate and adaptive immune responses. Immunostimulatory DCs are highly desired for the development of positive immunization techniques. DCs express functional NK1R; however, regardless of their potential DC-stimulatory function, the ability of NK1R agonists to promote immunostimulatory DCs remains unexplored. Here, we demonstrate that NK1R signaling activates therapeutic DCs capable of biasing type 1 immunity by inhibition of interleukin-10 (IL-10) synthesis and secretion, without affecting their low levels of IL-12 production. The potent type 1 effector immune response observed following cutaneous administration of NK1R-signaled DCs required their homing in skin-draining lymph nodes (sDLNs) where they induced inflammation and licensed endogenous-conventional sDLN-resident and -recruited inflammatory DCs to secrete IL-12. Our data demonstrate that NK1R signaling promotes immunostimulatory DCs, and provide relevant insight into the mechanisms used by neuromediators to regulate innate and adaptive immune responses.