Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Key Laboratory of Brain Function and Disease of Chinese Academy of Science, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei, China.
Front Immunol. 2018 Oct 17;9:2398. doi: 10.3389/fimmu.2018.02398. eCollection 2018.
Neurotransmitters have been shown to regulate immune responses, and thereby are critically related to autoimmune diseases. Here we showed that depletion of dopaminergic neurons significantly promoted activation of hepatic iNKT cells and augmented concanavalin A (Con A)-induced liver injury. The suppressive effect of dopamine on iNKT cells was mediated by D1-like receptor-PKA pathway. Clearance of gut microbiota by antibiotic cocktail reduced synthesis of dopamine in intestines and exacerbated liver damage, and that could be restored by recovery of gut microbiota or replenishment of D1-like receptor agonist. Our results demonstrate that peripheral dopamine controlled by gut microbes inhibits IL4 and IFNγ production in iNKT cells and suppresses iNKT cell-mediated hepatitis. Together, we propose a gut microbe-nervous system-immune system regulatory axis in modulating autoimmune hepatitis.
神经递质已被证明可调节免疫反应，因此与自身免疫性疾病密切相关。在这里，我们发现多巴胺能神经元的耗竭显著促进了肝内 iNKT 细胞的激活，并加剧了伴刀豆球蛋白 A（Con A）诱导的肝损伤。多巴胺对 iNKT 细胞的抑制作用是通过 D1 样受体-PKA 途径介导的。抗生素鸡尾酒清除肠道微生物群减少了肠道中多巴胺的合成，并加重了肝损伤，而这可以通过恢复肠道微生物群或补充 D1 样受体激动剂来恢复。我们的结果表明，由肠道微生物群控制的外周多巴胺抑制 iNKT 细胞中 IL4 和 IFNγ 的产生，并抑制 iNKT 细胞介导的肝炎。总之，我们提出了一个肠道微生物群-神经系统-免疫系统调节轴，用于调节自身免疫性肝炎。
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