Cell death and skin disease

Researchers have found that inflammatory skin diseases such as psoriasis may result from abnormal activation of apoptotic cell death pathways, which were previously thought to suppress inflammation.

Research by James Rickard, Associate Professor John Silke and colleagues from the Walter and Eliza Hall Institute focuses on how two cell death pathways, apoptosis and necroptosis, link to the development of inflammatory disease development.

Infected cells, cancerous cells or cells not needed by the body are instructed to die a programmed cell death called apoptosis. Apoptosis enables cells to die without affecting or harming surrounding cells and without mounting an immune response.

Another recently discovered form of cell death, necroptosis or inflammatory cell death, also instructs cells to die by a ‘programmed’ series of events - but there is a key difference.

The necroptotic cell death pathway involves the recruitment of immune cells and is important in the response to infection and disease.

Both types of cell death have been implicated in the development of immune disorders or inflammatory diseases such as psoriasis and Crohn’s disease.

In the study, the research team looked at how the loss of key molecules involved in necroptosis or apoptosis affected inflammation and inflammatory disease development.

“We were surprised to discover that apoptosis was the culprit in the development of inflammatory skin disease, while more extensive, system-wide inflammation such as in the liver and spleen was driven by necroptosis,” Rickard said. “This was quite unexpected, because apoptosis is not normally associated with inflammation.”

A better understanding of necroptosis could help to develop new treatments for inflammatory diseases.

“This work has provided us with clues about how existing medications for inflammatory diseases such as psoriasis work, suggesting their effectiveness could be related to their inhibition of apoptosis and necroptosis cell death pathways,” said Silke. “These existing medications are very effective; however, there are significant side effects.

Further research could help to develop new ways of treating these diseases with reduced side effects.

The study was published in the journal eLife.