Detox molecule triggers T-cell immune response

The antioxidant glutathione plays a larger role in fighting disease than was previously thought, writes Andrew Masterson.

A scanning electron micrograph of a healthy human T-cell.
National Institutes of Health

An antioxidant previously thought to be simply one of the body’s garbage collectors has been found to double as a critical switch for the immune system.

Glutathione, a molecule known to remove harmful metabolic byproducts such as free radicals, also functions to power up the immune system’s frontline bug-killers – a type of white blood cell known as T-cells.

This discovery, made by a team led by Dirk Brenner and published in the journal Immunity, opens the way to a whole new suite of possible treatments for a wide range of diseases.

Understanding the complex factors that affect the activity of T-cells is a key target for immunology research around the globe. The cells, like any type of predator, represent a mixed blessing.

In the best of circumstances they attack and defeat invading pathogens. In the worst, they attack the body itself.

“If its innate defences are overactive,” says Brenner, “then they turn against the body. This is what happens in auto-immune diseases like multiple sclerosis or arthritis.

“However if the defences are too weak, then infections cannot be handled, or body cells can proliferate uncontrolled and grow to form tumours, which can become life threatening.”

An infographic explaining the role of glutathione.
Luxembourg Institute of Health

Glutathione – which is catalysed by a gene known as Gclc – has previously been identified as playing an important role in tackling the byproducts of T-cell activity.

When the body is free from infection, T-cells exist in a state of low-energy readiness, rather like a squad of commandos during peacetime. When pathogens invade, however, the T-cells spring into action, revving up their metabolisms as they do so.

This increase in activity results in the production of potentially toxic waste – primarily free radicals and reactive oxygen species – and it is these that glutathione moves in to clean up.

Brenner’s team, however, identified a second role for the molecules. The research reveals that glutathione functions to trigger the T-cell activity in the first place, and is thus an important switch for the regulation of the immune system.

The discovery provides a valuable insight into the development of auto-immune diseases, which are linked to malfunctions in T-cell activity.

"If we understand the differences in the molecular mechanisms by which they stimulate their metabolism during defensive or auto-immune responses, then we can discover clues as to possible attack points for therapeutic agents regulating the immune response,” notes Brenner.

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