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

[Woolie]

Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines & emotional behavior Miyajima, M., et al.
Nature Immunology 18, 1342–1352 (2017)
doi:10.1038/ni.386

https://www.nature.com/articles/ni.3867

From the 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.

Okay, its mouse science. And these were genetically modified mice, and you can't ever be really sure whether the genetic modification is entirely selective to the thing you think it is (the excessive T cell activation). But kind of interesting nonetheless.

 

[Jonathan Edwards]

Okay, its mouse science. And these were genetically modified mice, and you can't ever be really sure whether the genetic modification is entirely selective to the thing you think it is (the excessive T cell activation). But kind of interesting nonetheless.

I doubt the result has anything particular to do with T cells. It shows that a large number of unregulated cells - most typically seen in cancer - eat up nutrients. People have observed cancer patients becoming cachectic for centuries. Many of these engineered mice have huge numbers of the unregulated cells. The MRL/lpr mouse has lymph nodes the size of cashew nuts, which scaled up to human size would weigh many kilograms.