New insight into inflammation and autoimmune diseases

In autoimmune diseases like rheumatoid arthritis and psoriasis, the body’s own defence mechanisms attack itself, causing inflammation and other problems.

Now a team of Australian scientists from La Trobe University and the University of Melbourne in collaboration with international researchers have uncovered a key protein that is involved in these and other autoimmune responses.

The protein, sharpin, has been known about for a decade, but its role in causing autoimmune diseases and inflammation has been unknown until now.

Writing in Nature, the researchers show that sharpin interacts with another protein complex that influence the tumour necrosis factor (TNF), a protein that plays a role in regulating the immune system can causing inflammation.

TNF plays a pivotal role in protecting the body against infection by bacteria, viruses and other pathogens. It does this by directing the immune system to spot rogue pathogens and then destroy them.

However, if TNF runs out of control, it can cause inflammation and autoimmune diseases, such as chronic proliferative dermatitis (cpdm), which is characterised by inflammatory skin lesions and defective lymphoid organogenesis.

The researchers found that mice deficient in sharpin developed cpdm. Yet if TNF was subsequently switched off, the dermatitis would clear up.

As such, the researchers suggest that sharpin plays a key role in regulating TNF and preventing it from running away and causing autoimmune disorders.

“This was a striking result, not least because TNF-controlled inflammation is central to a wide variety of different diseases from autoimmune diseases - like rheumatoid arthritis and psoriasis - to cancer,” said Associate Professor John Silke, from LaTrobe University.

It is hoped that a better understanding of the causes of inflammation and autoimmune diseases might lead to better treatments for rheumatoid arthritis and psoriasis and other ailments.

Co-author on the paper, Dr Andrew Webb, from the University of Melbourne, said the next step would be to use this new technique to further examine TNF and related pathways, to further understand the how these pathways function.

“A better understanding of these pathways will ultimately lead to better therapies for diseases that involve immune dysfunction,” he said.

The paper was published today in Nature.