Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior

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 HonjoSidonia Fagarasan

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36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1342-1352
Number of pages11
JournalNature Immunology
Volume18
Issue number12
DOIs
Publication statusPublished - 2017 Nov 16

ASJC Scopus subject areas

  • Immunology

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    Miyajima, M., Zhang, B., Sugiura, Y., Sonomura, K., Guerrini, M. M., Tsutsui, Y., Maruya, M., Vogelzang, A., Chamoto, K., Honda, K., Hikida, T., Ito, S., Qin, H., Sanuki, R., Suzuki, K., Furukawa, T., Ishihama, Y., Matsuda, F., Suematsu, M., ... Fagarasan, S. (2017). Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior. Nature Immunology, 18(12), 1342-1352. https://doi.org/10.1038/ni.3867