A trio of proteins – including one called TWEAK - may hold keys to psoriasis causes and treatment

Nov. 23, 2021

A study conducted by the Center for Autoimmunity and Inflammation and supported by the National Institutes of Health, has found a key protein responsible, researchers believe, in causing psoriasis.

About 7.5 million Americans suffer from psoriasis, an autoimmune disease, which shows as patches of red, inflamed skin and painful, scaly rashes. Although there are effective treatments for psoriasis, not everyone responds to the therapies—and for many, the relief is temporary.

The protein, called TWEAK, damages skin cells in psoriasis patients. The study used mice and human skin cells. Its findings suggest, according to a press release, that targeting TWEAK may help control the disease.   

The Croft Lab captured how the proliferation of skin cells, as seen in psoriasis (indicated with purple staining), decreased when TWEAK activity was blocked (Image courtesy Rinkesh Gupta.)

The findings build on the Croft Lab’s previous work showing that TWEAK can interact with the most common type of skin cell, called a keratinocyte. By investigating TWEAK-deficient mice, the researchers found that TWEAK is a driver of inflammation in a model of psoriasis.

The new study shows that TWEAK does not work alone. By studying human keratinocytes, the researchers discovered that TWEAK teams up with two other proteins, called tumor necrosis factor (TNF) and interleukin-17 (IL-17), to trigger inflammation. This trio appears to control the production of inflammatory molecules and the expression of additional inflammation-associated proteins in patients with psoriasis.

To test this, the researchers used a mouse model of psoriasis to compare how well a TWEAK-inhibitor measured up to therapies inhibiting IL-17 or TNF.

The study’s findings are especially encouraging, according to researchers, because TNF and IL-17 are both FDA-approved drug targets for psoriasis.

Human clinical trials remain to be done, but the study team is hopeful that development of TWEAK inhibitors could prove effective as therapies for many types of skin diseases.

La Jolla Institute for Immunology press release