AsianScientist (Nov. 1, 2017) – In a study published in Nature Immunology, scientists from the RIKEN Center for Integrative Medical Sciences in Japan have found that the prolonged activation of T-cells results in increased anxiety and fear responses.
T-cells are immune cells that help to protect the body from infections and cancer. It is currently known that individual T-cells change their metabolism to meet their energy needs after being activated, but the systemic metabolic effect of sustained activation of the immune system has remained unexplored.
In this study, researchers in Japan looked at T-cell activation in genetically engineered mice lacking a protein called PD-1 on the surface of their cells. PD-1 is necessary for inhibiting the activity of T-cells. They observed that T-cells remained activated in mice without the receptor, similar to those in the immune systems of people with certain types of autoimmune disease.
In these PD-1 deficient mice, they found that amino acids—molecules that are used to build proteins—were depleted in the blood. Meanwhile, the amount of amino acids in T-cells was elevated.
The team then tracked and imaged amino acids in many organs. They found that the depletion of amino acids from the blood was taking place due to the accumulation of amino acids in activated T-cells in the lymph nodes, showing that strong or long-lasting immune responses can cause metabolic changes elsewhere in the body.
The remaining question was whether this depletion of amino acids was actually having any systemic effect. By analyzing the biochemistry of the brain, they found that the systemic decrease in the amino acids tryptophan and tyrosine in the blood led to lower amounts available in the brain.
The lack of these amino acids in the brain limited the production of the neurotransmitters serotonin and dopamine, which affect emotions, motivation and fear. The researchers found that the depletion of serotonin in mice without PD-1 resulted in behavioral changes dominated by anxiety and exacerbated fear responses, which could be remedied by providing a diet rich in amino acids.
“Together these data indicate that excessive activation of T-cells causes a systemic metabolomic shift with consequences that extend beyond the immune system,” said Dr. Michio Miyajima, one of the authors of the study.
“We were fascinated to see that this happens, as it revealed the power of the immune system to influence many aspects of the body’s physiology besides infection and immunity. It will be interesting in the future to investigate whether the trigger of fear and anxiety by T-cell activation is merely a side effect of the process, or whether there is an evolutionary benefit of this adaptation,” said Dr. Sidonia Fagarasan, the leader of the group.
“We would also like to further investigate these changes, as the blockade of PD-1 is being investigated as an anti-cancer therapy, and it is important to understand if this could have behavioral changes such as increases in anxiety,” she added.
The article can be found at: Miyajima et al. (2017) Metabolic Shift Induced by Systemic Activation of T Cells in PD-1-deficient Mice Perturbs Brain Monoamines and Emotional Behavior.
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Source: RIKEN; Photo: Shutterstock.
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