The Tachykinins Substance P and Hemokinin-1 Favor the Generation of Human Memory Th17 Cells by Inducing IL-1β, IL-23, and TNF-Like 1A Expression by Monocytes
The Tachykinins Substance P and Hemokinin-1 Favor the Generation of Human Memory Th17 Cells by Inducing IL-1β, IL-23, and TNF-Like 1A Expression by Monocytes
复制标题
DOI：
10.4049/jimmunol.1002535
复制
发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Jeannin, Pascale
中科院分区：
文献类型：
--
作者：
Cunin, Pierre;Caillon, Antoine;Jeannin, Pascale
神经系统通过释放神经因子如神经肽来影响免疫反应。其中，速激肽P物质（SP）通过神经激肽1受体（NK-1 R）发出信号，该受体由各种免疫细胞表达。因此，我们分析了速激肽是否可能参与人CD 4（+）Th细胞极化。我们报道SP和hemokinin-1（HK-1）上调人记忆性CD 4（+）T细胞产生IL-17 A和IFN-γ，而不影响IL-4和IL-10的产生。SP和HK-1将非Th 17定向的CD 4（+）记忆T细胞转换为真正的Th 17细胞和Th 1/Th 17细胞。相反，SP和HK-1不调节初始CD 4（+）T细胞的极化。SP和HK-1诱导的Th 17细胞生成通过NK-1 R介导，需要单核细胞的存在。SP和HK-1触发IL-1 β、IL-6和TNF-α产生，上调IL-23产生，并增强单核细胞表面TNF-样1A表达。中和实验证明IL-1 β、IL-23和TNF样1A参与SP和HK-1诱导的Th 17细胞。速激肽家族的其他成员，神经激肽A和B，对初始和记忆T细胞的分化没有影响。因此，这些结果表明，SP和HK-1是新的Th 17细胞诱导因子，可以局部作用于记忆T细胞，以放大炎症反应。免疫学杂志，2011，186：4175-4182。
The nervous system influences immune responses through the release of neural factors such as neuropeptides. Among them, the tachykinin substance P (SP) signals via the neurokinin 1 receptor (NK-1R), which is expressed by various immune cells. We thereby analyzed in this paper whether tachykinins may participate in human CD4(+) Th cell polarization. We report that SP and hemokinin-1 (HK-1) upregulate IL-17A and IFN-gamma production by human memory CD4(+) T cells without affecting IL-4 and IL-10 production. SP and HK-1 switch non-Th17-committed CD4(+) memory T cells into bona fide Th17 cells and Th1/Th17 cells. In contrast, SP and HK-1 do not modulate the polarization of naive CD4(+) T cells. SP- and HK-1-induced Th17 cell generation is mediated through NK-1R and requires the presence of monocytes. SP and HK-1 trigger IL-1 beta, IL-6, and TNF-alpha production, upregulate IL-23 production, and enhance TNF-like 1A expression on monocyte surface. Neutralization experiments demonstrated that IL-1 beta, IL-23, and TNF-like 1A are involved in the SP- and HK-1-induced Th17 cell. The other members of the tachykinin family, neurokinins A and B, have no effect on the differentiation of naive and memory T cells. These results thereby show that SP and HK-1 are novel Th17 cell-inducing factors that may act locally on memory T cells to amplify inflammatory responses. The Journal of Immunology, 2011, 186: 4175-4182.