VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4+ T cells
VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4+ T cells
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DOI：
10.1189/jlb.1203626
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发表时间：
2004-06-01
影响因子：
5.5
通讯作者：
Ganea, D
中科院分区：
文献类型：
--
作者：
Delgado, M;Reduta, A;Ganea, D
神经末梢和/或免疫细胞在淋巴器官内释放的神经肽血管活性肠肽（VIP）和垂体腺苷酸环化酶激活多肽（PACAP）通过抑制巨噬细胞诱导的炎症反应和促进T细胞发挥显着的抗炎作用2型（Th 2）反应。然而，树突状细胞（DC）而不是巨噬细胞通常是主要的抗原呈递细胞，并且是先天性免疫和适应性免疫之间的联系。VIP/PACAP在DC发育和功能中的作用大多未知。在这里，我们报告说，骨髓来源的DC表达VIP/ PACAP受体，VIP和PACAP对未成熟DC（iDC）和脂多糖（LPS）处理的DC产生不同的影响。在iDC中，VIP/ PACAP上调CD 86表达，并使其能够在体内和体外刺激T细胞增殖和分化为Th 2效应子。相反，VIP/PACAP下调LPS刺激的DC中的CD 80/CD 86表达，并强烈降低其刺激T细胞增殖和分泌Th 1和Th 2细胞因子的能力。VIP/PACAP对iDC和LPS刺激的DC的作用主要通过VIP受体1介导。这些结果表明，神经肽如VIP和PACAP可以不同地影响iDC和成熟DC的功能。在没有持续的免疫应答的情况下，VIP/PACAP有助于Th 2型免疫的启动，而在存在完全爆发的炎症反应的情况下，VIP/PACAP充当抗炎剂。
The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) released within lymphoid organs from nerve terminals and/or immune cells play a significant, anti-inflammatory role by inhibiting macrophage-induced inflammatory reactions and promoting T helper cell type 2 (Th2) responses. However, dendritic cells (DC) and not macrophages often are the major antigen-presenting cells and link between innate and adaptive immunity. The role of VIP/PACAP in DC development and function is mostly unknown. Here, we report that bone marrow-derived DC express VIP/ PACAP receptors and that VIP and PACAP exert a differential effect on immature DC (iDC) and lipopolysaccharide (LPS)-treated DC. In iDC, VIP/ PACAP up-regulates CD86 expression and enables them to stimulate T cell proliferation and differentiation into Th2 effectors in vivo and in vitro. In contrast, VIP/PACAP down-regulates CD80/CD86 expression in LPS-stimulated DC and strongly reduces their capacity to stimulate T cell proliferation and secretion of Th1 and Th2 cytokines. The VIP/PACAP effects on iDC and LPS-stimulated DC are mediated primarily through the VIP receptor 1. These results indicate that neuropeptides such as VIP and PACAP can differentially affect the function of iDC and mature DC. In the absence of an ongoing immune response, VIP/PACAP contributes to the initiation of Th2-type immunity, whereas in the presence of a full-blown, inflammatory reaction, VIP/PACAP act as anti-inflammatory agents.