One amino acid fuels immune cells that attack the body
The immune system can turn against its own host. That is the core of autoimmune diseases like multiple sclerosis. New research shows that removing a single amino acid weakens the immune cells responsible for the attack.
T cells are white blood cells that direct the immune response. In autoimmune diseases, some T cells target healthy tissue. In multiple sclerosis (MS), they attack myelin sheaths, the protective coating of nerve fibres. Scientists have been searching for ways to suppress only these harmful T cells, without shutting down the entire immune system.
Asparagine as fuel for self-attacking cells
The study, published in eLife, shows that the amino acid asparagine is essential for the activation and division of CD4+ T cells. CD4+ T cells are a group of immune cells that play a coordinating role in the immune response. Without asparagine, energy production in the mitochondria, the powerhouses of cells, falls, and the cells produce fewer inflammatory signalling proteins (cytokines).
In mouse models of autoimmune brain inflammation (experimental autoimmune encephalomyelitis, EAE), a standard system for MS research, depleting asparagine substantially reduced disease severity. T cells grown without asparagine were less capable of attacking the nervous system. Therapeutic administration of an asparagine-lowering agent mid-disease also had a dampening effect on severity.
A potential new therapeutic target
These are results from animal experiments. Translation to humans requires further studies. The mechanism is striking, however: asparagine is a non-essential amino acid, meaning the body can produce it on its own. Yet for actively dividing immune cells, it proves critical. The researchers suggest that selectively lowering asparagine in the vicinity of autoreactive T cells, the T cells that target the body’s own tissue, could be a therapeutic strategy with fewer side effects than broad immune suppression.
From a longevity perspective, this is relevant: autoimmune conditions increase with age and contribute to immune system aging. Methods to selectively dampen autoreactive cells could in time find broader applications.
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