Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior
Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior
复制标题
DOI：
10.1038/ni.3867
复制
发表时间：
2017-12-01
影响因子：
30.5
通讯作者：
Fagarasan, Sidonia
中科院分区：
文献类型：
--
作者：
Miyajima, Michio;Zhang, Baihao;Fagarasan, Sidonia
T细胞在被激活后重组其代谢谱，但持续激活免疫系统的系统代谢效应仍未被探索。在这里，我们报告了缺乏抑制受体PD-1的Pdcd1(-/-)小鼠增强的T细胞反应，诱导了以氨基酸耗竭为特征的代谢血清特征。我们发现血清中氨基酸的耗竭是由于淋巴结中激活的Pdcd1(-/-)T细胞中的氨基酸积累所致。色氨酸和酪氨酸的全身性减少导致大脑中神经递质5-羟色胺和多巴胺的严重不足，导致以焦虑样行为为主的行为变化，并加剧恐惧反应。总而言之，这些数据表明，T细胞的过度激活会导致全身性代谢改变，其后果超出免疫系统。
T cells reorganize their metabolic profiles after being activated, but the systemic metabolic effect of sustained activation of the immune system has remained unexplored. Here we report that augmented T cell responses in Pdcd1(-/-)mice, which lack the inhibitory receptor PD-1, induced a metabolic serum signature characterized by depletion of amino acids. We found that the depletion of amino acids in serum was due to the accumulation of amino acids in activated Pdcd1(-/-)T cells in the lymph nodes. A systemic decrease in tryptophan and tyrosine led to substantial deficiency in the neurotransmitters serotonin and dopamine in the brain, which resulted in behavioral changes dominated by anxiety-like behavior and exacerbated fear responses. Together these data indicate that excessive activation of T cells causes a systemic metabolomic shift with consequences that extend beyond the immune system.