Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil.
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02458, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Rep. 2019 Sep 17;28(12):3120-3130.e5. doi: 10.1016/j.celrep.2019.08.042.
Noradrenaline (NE), the main neurotransmitter released by sympathetic nerve terminals, is known to modulate the immune response. However, the role of the sympathetic nervous system (SNS) on the development of autoimmune diseases is still unclear. Here, we report that the SNS limits the generation of pathogenic T cells and disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). β2-Adrenergic receptor (Adrb2) signaling limits T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER). Accordingly, the lack of Adrb2 signaling in immune cells is sufficient to abrogate the suppressive effects of SNS activity, resulting in increased pathogenic T cell responses and EAE development. Collectively, these results uncover a suppressive role for the SNS in CNS autoimmunity while they identify potential targets for therapeutic intervention.
去甲肾上腺素（NE）是交感神经末梢释放的主要神经递质，已知其可调节免疫反应。然而，交感神经系统（SNS）在自身免疫性疾病发展中的作用尚不清楚。在这里，我们报告 SNS 限制了多发性硬化症（MS）实验性自身免疫性脑脊髓炎（EAE）模型中致病性 T 细胞的产生和疾病的发展。β2-肾上腺素能受体（Adrb2）信号通过抑制诱导型 cAMP 早期阻遏物（ICER）介导的 IL-2、IFN-γ 和 GM-CSF 产生，限制 EAE 中的 T 细胞自身免疫。因此，免疫细胞中缺乏 Adrb2 信号足以消除 SNS 活性的抑制作用，导致致病性 T 细胞反应增加和 EAE 发展。总的来说，这些结果揭示了 SNS 在中枢神经系统自身免疫中的抑制作用，同时也确定了潜在的治疗干预靶点。
