Lupus clues from cellular ‘power stations’

Researchers at Imperial College London have revealed crucial insights into the medical condition systemic lupus erythematosus (SLE).

Lupus is a life-long autoimmune disease, mainly affecting young women from ethnic minority groups. The condition causes the body’s immune system to malfunction and start attacking different organs, especially the skin and kidneys. The initial causes of lupus are unknown, but infections are thought to play a role.

Here we show that type I interferons cause the cellular power stations, called mitochondria, to malfunction. Professor Marina Botto Study author

Previous studies from the same Imperial College researchers have suggested that immune cells called CD8 T cells, which normally help to destroy threats to the body such as viruses, appear to malfunction in SLE patients.

This may play a role in the immune system spiralling out of control.

In the latest study, published in Nature Communications, scientists have revealed insights into how these CD8 T cells malfunction.

The study, which looked at immune cells from both healthy individuals and lupus patients, found that these T cells have certain genes switched ‘on’ by specific immune proteins, called type I interferons.

These proteins are usually only present during viral infections – their role is to signal to the body it is being invaded by a virus.

However, in lupus patients the interferons activate genes in the CD8 T cells that alter how the cells make their energy to survive. As result of these changes the cells die more easily.

Professor Marina Botto, lead author and Head of the Department of Immunology and Inflammation at Imperial, explained: ‘The type I interferons are known to be produced by the body during virus infections. Although the initial trigger for lupus remains unknown, the condition could be sustained by viral infections that trigger an expansion of the CD8 T cells. Here we show that the type I interferons cause the cellular power stations, called mitochondria, to malfunction. This malfunction of the mitochondria reduces the life-span of the CD8 T cells and may fuel the disease.’

The research team add that the new insights may help develop future treatments for the condition.

This work was supported by the Wellcome Trust and National Institute for Health Research (NIHR) Imperial Biomedical Research Centre

Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus‘ is published in Nature Communications

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