論文

査読有り
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
  • Michio Miyajima
  • Baihao Zhang
  • Yuki Sugiura
  • Kazuhiro Sonomura
  • Matteo M. Guerrini
  • Yumi Tsutsui
  • Mikako Maruya
  • Alexis Vogelzang
  • Kenji Chamoto
  • Kurara Honda
  • Takatoshi Hikida
  • Satomi Ito
  • Hongyan Qin
  • Rikako Sanuki
  • Keiichiro Suzuki
  • Takahisa Furukawa
  • Yasushi Ishihama
  • Fumihiko Matsuda
  • Makoto Suematsu
  • Tasuku Honjo
  • Sidonia Fagarasan
  • 全て表示

18
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
DOI
https://doi.org/10.1038/ni.3867
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29058703
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000415324900012&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/ni.3867
  • ISSN : 1529-2908
  • eISSN : 1529-2916
  • PubMed ID : 29058703
  • Web of Science ID : WOS:000415324900012

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