How to beat psoriasis at its own game

Scientists have now derived a compound from the body's own immune cells and used it to successfully treat psoriasis in mice. The way the compound works with the body's immune system makes it a potential candidate for treating other autoimmune disorders as well, such as rheumatoid arthritis and multiple sclerosis.

Psoriasis is an autoimmune disease in which the body's immune system does not recognize its own tissue and starts attacking it.

This accelerates the growth cycle of skin cells, which causes them to accumulate in excess over the skin's surface.

In the United States, around 6.7 million adults have this condition, for which there is yet no cure.

But new research offers hope, as scientists at the Washington University School of Medicine in St. Louis, MO, reveal a new way to use the body's own immunity to fight psoriasis.

The researchers — led by Maxim Artyomov, an assistant professor of pathology and immunology at the university — found that a compound blocks an inflammatory pathway that is involved in many other autoimmune disorders.

The findings were published in the journal Nature.

Itaconate and the 'dark side' of IL-17

In previous research, a team led by the same Artyomov showed that inflammatory immune cells called macrophages produce significant amounts of itaconate when they detect bacteria.

They have also shown that, interestingly, itaconate has an anti-inflammatory effect when these macrophages are activated.

To illuminate the mechanisms behind this observation, they treated macrophages from both mice and humans with dimethyl itaconate, which is a version of itaconate that makes it easier to permeate through the cells' membrane.

They revealed that dimethyl itaconate inhibits an inflammatory pathway called IL-17. This pathway is key in our body's ability to fight off pathogens, but its "dark side" is that it facilitates autoimmune destruction in conditions such as multiple sclerosis (MS), psoriasis, and rheumatoid arthritis.

In this case, specifically, the new compound inhibited IL-17 cytokines by decreasing a protein called IkappaBzeta.

Previous studies have suggested that IkappaBzeta genetic variations may raise the risk of psoriasis, so the researchers hypothesized that lowering this protein with itaconate would treat psoriasis.

The hidden powers of a small molecule

In order to test this hypothesis, the scientists induced psoriasis-like symptoms in the rodents' ears. They then treated the mice with dimethyl itaconate daily for a week. Another group of mice only received a placebo.

After a week, the mice that received the intervention had normal, healthy-looking ears, whereas the placebo mice displayed signs of worsening psoriasis.

"We are taking advantage of the body's own anti-inflammatory power and showing that it can help in real situations when your own immune system is hurting you," says Artyomov.

He and his colleagues have already started examining the effect of itaconate on a mouse model of MS.

"Since we first linked itaconate to inflammatory cell activation in 2016, it has been surprising us," Artyomov says. "Everyone thought that if it is produced by inflammatory cells it should fight infection, but no — it's anti-inflammatory."

"Now we know that itaconate compounds can help with autoimmune diseases, specifically in psoriasis and potentially in multiple sclerosis. This small molecule is turning out to be really powerful."

Maxim Artyomov