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

Miyajima, Michio; Zhang, Baihao; Sugiura, Yuki; Sonomura, Kazuhiro; Guerrini, Matteo M; Tsutsui, Yumi; Maruya, Mikako; Vogelzang, Alexis; Chamoto, Kenji; Honda, Kurara; Hikida, Takatoshi; Ito, Satomi; Qin, Hongyan; Sanuki, Rikako; Suzuki, Keiichiro; Furukawa, Takahisa; Ishihama, Yasushi; Matsuda, Fumihiko; Suematsu, Makoto; Honjo, Tasuku; Fagarasan, Sidonia.
Nat Immunol; 18(12): 1342-1352, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29058703
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.
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