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Dead cell removal process gives lupus hint

Lupus hint A molecule that is crucial to cleaning up dead cells in mice could shed light on autoimmune diseases such as lupus in humans, researchers say.

Dr Terry Means, an assistant professor of medicine at Harvard Medical School, and colleagues ,report their findings today in Nature Immunology.

Cells undergoing apoptosis (programmed cell death) are normally cleaned up and removed by immune system cells.

But in diseases such as lupus, scientists believe clearance of so-called 'apoptotic cells' can go wrong, and dead cells build up and trigger the immune system to start making antibodies against them, and other parts of the healthy body.

Antibodies get deposited in tissues, such as the kidneys, and this leads to inflammation, and other symptoms.

Receptor studies

Means and colleagues noticed that in the worm Caenorhabditis elegans a receptor called CED-1 mediates dead cell removal and in mammals there was a related receptor called SCARF1, so they wondered whether SCARF1 might be involved in producing symptoms of lupus.

SCARF1 binds a component in the serum called C1q, which helps dead cells to be recognised by garbage-collecting immune cells.

Means and colleagues created genetically modified mice that lacked the gene for the SCARF1 receptor.

"We found that after about a month or two, dead cells started accumulating in the circulation and tissues of these mice because they were not being removed properly," say Means.

"At four months of age, they develop auto-antibodies, skin disease, typically on the face and back, and they got kidney damage with proteinuria in their urine. These are all classic symptoms of lupus in humans."

"SCARF1 is the first C1q receptor that seems to be important in the removal of dead cells," says Means.

While there are other mechanisms involved in clearance of apoptotic cells, the researchers believe the receptor is responsible for clearing of 40 to 70 per cent of them.

Human lupus

The researchers now want to see whether the findings can help in human lupus patients.

"Dead cell removal likely occurs by a similar process in humans and mice," says Means.

"We showed that human SCARF1 binds and recognises dead cells. What we don't know yet is whether human lupus patients have defects in SCARF1 expression or function."

But, he says genetic studies should clarify this within a few years.

"Therapeutically we could find ways to increase SCARF1 expression or maybe make a therapeutic SCARF1 protein that we could use to coat dead cells to help clear them more efficiently," says Means.

'Nice paper'

Australian lupus researcher Professor Fabienne Mackay of Monash University in Melbourne says it's "a nice paper.

"I really like it. It's shedding new light on that system," she says.

But like Mackay, another Australian lupus researcher, Professor Tom Gordon from Flinders University in Adelaide, emphasises the research is in only in mice.

"I think we're still a long way from knowing whether this type of study will lead to new therapeutics that might help lupus patients," says Gordon.

He says none of these mouse models produce exactly the same sort of lupus seen in humans.

"It would be very interesting if studies on the genetics of lupus did detect mutations of this receptor. That would start to bring it together."

He says the findings could also be relevant to another autoimmune disease called Sjögren's syndrome.