First Author | Miyajima M | Year | 2017 |
Journal | Nat Immunol | Volume | 18 |
Issue | 12 | Pages | 1342-1352 |
PubMed ID | 29058703 | Mgi Jnum | J:258412 |
Mgi Id | MGI:6142552 | Doi | 10.1038/ni.3867 |
Citation | Miyajima M, et al. (2017) Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior. Nat Immunol 18(12):1342-1352 |
abstractText | 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. |