Format

Send to

Choose Destination
Nat Immunol. 2017 Dec;18(12):1342-1352. doi: 10.1038/ni.3867. Epub 2017 Oct 23.

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

Author information

1
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.
2
Department of Immunology and Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
3
Department of Biochemistry and Integrative Biology, Keio University, Tokyo, Japan.
4
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University, Kyoto, Japan.
5
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
6
Department of Medical Genetics and Developmental Biology, 4th Military Medical University, Xi'an, China.
7
Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, Japan.
8
Department of Molecular and Cellular Bioanalyses, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

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.

PMID:
29058703
DOI:
10.1038/ni.3867
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center