2017年12月
Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior
NATURE IMMUNOLOGY
- 巻
- 18
- 号
- 12
- 開始ページ
- 1342
- 終了ページ
- +
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ni.3867
- 出版者・発行元
- NATURE PUBLISHING GROUP
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.
- リンク情報
- ID情報
-
- DOI : 10.1038/ni.3867
- ISSN : 1529-2908
- eISSN : 1529-2916
- PubMed ID : 29058703
- Web of Science ID : WOS:000415324900012