Department of Anesthesiology and Intensive Care Medicine, Molecular Intensive Care Medicine, University Hospital Tübingen, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
Department of Pediatric Cardiology and Critical Care, Carl-Neuberg-Str. 1, Hannover Medical School, 30625, Hannover, Germany.
Nat Commun. 2019 Feb 7;10(1):633. doi: 10.1038/s41467-019-08328-5.
The bidirectional communication between the immune and nervous system is important in regulating immune responses. Here we show that the adrenergic nerves of sympathetic nervous system orchestrate inflammation resolution and regenerative programs by modulating repulsive guidance molecule A (RGM-A). In murine peritonitis, adrenergic nerves and RGM-A show bidirectional activation by stimulating the mutual expression and exhibit a higher potency for the cessation of neutrophil infiltration; this reduction is accompanied by increased pro-resolving monocyte or macrophage recruitment, polymorphonucleocyte clearance and specialized pro-resolving lipid mediators production at sites of injury. Chemical sympathectomy results in hyperinflammation and ineffective resolution in mice, while RGM-A treatments reverse these phenotypes. Signalling network analyses imply that RGM-A and β2AR agonist regulate monocyte activation by suppressing NF-κB activity but activating RICTOR and PI3K/AKT signalling. Our results thus illustrate the function of sympathetic nervous system and RGM-A in regulating resolution and tissue repair in a murine acute peritonitis model.
免疫系统和神经系统之间的双向通讯对于调节免疫反应很重要。在这里，我们表明交感神经系统的肾上腺素能神经通过调节排斥导向分子 A（RGM-A）来协调炎症的消退和再生程序。在小鼠腹膜炎中，肾上腺素能神经和 RGM-A 通过刺激相互表达而表现出双向激活，并显示出更强的停止中性粒细胞浸润的能力；这种减少伴随着更多的促解决单核细胞或巨噬细胞募集、多形核白细胞清除和损伤部位特异性促解决脂质介质的产生。化学交感神经切除术会导致小鼠过度炎症和无效的消退，而 RGM-A 治疗则逆转了这些表型。信号网络分析表明，RGM-A 和β2AR 激动剂通过抑制 NF-κB 活性但激活 RICTOR 和 PI3K/AKT 信号来调节单核细胞的激活。因此，我们的研究结果说明了交感神经系统和 RGM-A 在调节小鼠急性腹膜炎模型中的炎症消退和组织修复中的功能。
