β2-Adrenergic agonists bias TLR-2 and NOD2 activated dendritic cells towards inducing an IL-17 immune response.
β2-Adrenergic agonists bias TLR-2 and NOD2 activated dendritic cells towards inducing an IL-17 immune response.
复制标题
β2-肾上腺素能激动剂偏置TLR-2和NOD2激活树突状细胞诱导IL-17免疫反应。
DOI：
10.1016/j.cyto.2011.05.013
复制
发表时间：
2011-09
期刊：
影响因子：
3.8
通讯作者：
Maestroni, Georges
中科院分区：
文献类型：
--
作者：
Manni, Michela;Granstein, Richard D.;Maestroni, Georges
这项研究测试了这样的假设：DC 上 β2 肾上腺素受体的激活会影响 NOD2 信号传导及其与 Toll 样受体 2 的串扰，从而导致 Th 细胞启动能力改变。 Th17 细胞是新发现的 CD4+ T 细胞谱系，参与防御细胞外细菌，也与自身免疫性疾病有关。适应性免疫反应的启动和极化是由 DC 介导的先天免疫识别控制的。先前的研究表明，肾上腺素能受体调节 DC 的细胞因子产生并影响其 Th 细胞启动能力。我们发现，β2-肾上腺素受体激动剂沙丁胺醇增强了用核苷酸结合寡聚结构域 2 配体胞壁酰二肽刺激的小鼠骨髓来源的 DC 中 IL-6 的产生。然而，当添加 Toll 样受体 2 配体 Pam3CysSK4 时，沙丁胺醇会抑制 IL-12，但不会改变 IL-6 和 IL-23 的表达。基因表达分析表明，沙丁胺醇抑制 p40 亚基以及 IL-12p35，同时刺激 IL-23p19 和 IL-6。因此，β2-肾上腺素受体调节细胞因子的产生，导致 Th17 细胞启动细胞因子模式。事实上，当在沙丁胺醇存在下用胞壁酰二肽或 Pam3CysSK4+胞壁酰二肽刺激的抗原脉冲 DC 用于体内免疫时，根据 IL-17 和 IFN-γ 的产生评估，所得 Th17/Th1 细胞比率增加。此外，皮内注射去甲肾上腺素和 Pam3CysSK4+ 胞壁酰二肽可增加 Th17 对免疫原性蛋白的反应，并且这种效应可被 β2-肾上腺素受体拮抗剂逆转。因此，β2-肾上腺素受体可能参与调节细胞外细菌的防御和炎症性疾病的发病机制。
This study tested the hypothesis that activation of β2-adrenoceptors on DCs influences NOD2 signaling along with its cross-talk with Toll-like receptor-2 resulting in altered Th cell priming ability. Th17 cells are a newly discovered lineage of CD4+ T cells involved in defense against extracellular bacteria and also implicated in autoimmune disorders. Initiation and polarization of the adaptive immune response is controlled by innate immune recognition mediated by DCs. Previous studies demonstrated that adrenergic receptors modulate cytokine production by DCs and affect their Th cell priming ability. We show that the β2-adrenoceptor agonist salbutamol enhanced IL-6 production in murine bone marrow-derived DCs stimulated with the nucleotide-binding oligomerization domain 2 ligand muramyl dipeptide. However, when the Toll-like receptor-2 ligand Pam3CysSK4 was added, salbutamol inhibited IL-12 but did not alter IL-6 and IL-23 expression. Gene expression analysis showed that salbutamol inhibited the p40 subunit as well as IL-12p35, while IL-23p19 and IL-6 were stimulated. Therefore, β2-adrenoceptors modulated cytokine production resulting in a Th17 cell priming cytokine pattern. Indeed, when antigen-pulsed DCs stimulated by muramyl dipeptide or Pam3CysSK4+muramyl dipeptide in the presence of salbutamol were used for in vivo immunization, the resulting Th17/Th1 cell ratio was increased as evaluated by IL-17 and IFN-γ production. In addition, intradermal injection of norepinephrine along with Pam3CysSK4+muramyl dipeptide increased the Th17 response to an immunogenic protein and this effect was reversed by a β2-adrenoceptor antagonist. Thus, β2-adrenoceptors may be involved in the regulation of defense against extracellular bacteria and the pathogenesis of inflammatory diseases.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5.5
作者：
Ortega, Consuelo;Fernandez-A, Silvia;Santamaria, Manuel
通讯作者：
Santamaria, Manuel
影响因子：
4.4
作者：
Seiffert, K;Hosoi, J;Granstein, RD
通讯作者：
Granstein, RD
DOI：
10.1084/jem.20061401
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Schnyder-Candrian S;Togbe D;Couillin I;Mercier I;Brombacher F;Quesniaux V;Fossiez F;Ryffel B;Schnyder B
通讯作者：
Schnyder B
影响因子：
15.1
作者：
Manni, Michela;Maestroni, Georges J. M.
通讯作者：
Maestroni, Georges J. M.