RRC ID 49605
Author Miyajima M, Zhang B, Sugiura Y, Sonomura K, Guerrini MM, 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, Honjo T, Fagarasan S.
Title Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior.
Journal Nat Immunol
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.
Volume 18(12)
Pages 1342-1352
Published 2017-12-1
DOI 10.1038/ni.3867
PII ni.3867
PMID 29058703
MeSH Amino Acids / blood Animals Anxiety / physiopathology* Behavior, Animal / physiology* Brain / metabolism Dopamine / deficiency Fear / physiology* Interferon-gamma / blood Kynurenine / blood Lymph Nodes / metabolism Lymphocyte Activation / immunology* Mice Mice, Inbred C57BL Mice, Knockout Programmed Cell Death 1 Receptor / deficiency Programmed Cell Death 1 Receptor / genetics* Serotonin / deficiency T-Lymphocytes / immunology* T-Lymphocytes / metabolism Tryptophan / metabolism Tyrosine / metabolism
IF 20.479
Times Cited 36
Mice RBRC02142