@article{b6029e8d3392445bbffd92d0e2ce1dbf,
title = "Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior",
abstract = "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.",
author = "Michio Miyajima and Baihao Zhang and Yuki Sugiura and Kazuhiro Sonomura and Guerrini, {Matteo M.} and Yumi Tsutsui and Mikako Maruya and Alexis Vogelzang and Kenji Chamoto and Kurara Honda and Takatoshi Hikida and Satomi Ito and Hongyan Qin and Rikako Sanuki and Keiichiro Suzuki and Takahisa Furukawa and Yasushi Ishihama and Fumihiko Matsuda and Makoto Suematsu and Tasuku Honjo and Sidonia Fagarasan",
note = "Funding Information: We thank S. Yamamoto, S. Oonawa and Y. Doi for technical help; S. Kawamoto, T. Chaya, and T. Kozuka for the help with metabolome and brain dissection and preparations; S. Narumiya, T. Sato and K. Tanaka for discussions and suggestion; Y. Iwakura (Tokyo University of Science) and M. Kubo (IMS RIKEN) for Ifng−/− mice; B. Malissen (Centre d{\textquoteright}Immunologie de Marseille-Luminy) for Cd3e−/− mice; and N. Lonberg (Bristol-Myers Squibb) for anti-PD-1. Supported by Japan Agency for Medical Research and Development–Core Research for Evolutional Science and Technology (14532135 to S.F.), Japan Agency for Medical Research and Development (145208 and 16770835 to T.H.) and the Cell Science Foundation (K.C). Publisher Copyright: {\textcopyright} 2017 Nature America Inc,part of Springer Nature. All rights reserved.",
year = "2017",
month = nov,
day = "16",
doi = "10.1038/ni.3867",
language = "English",
volume = "18",
pages = "1342--1352",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",
}