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Inflammatory pathway in lichen planus identified, possible target for JAK inhibitors

Lichen planus photo by: James Heilman, MD, via Wikimedia Commons

Researchers have discovered that lichen planus appears to be characterized by a type II interferon (IFN) inflammatory response in the skin, a process dependent on Janus kinase 2 (JAK2). This finding suggests that existing JAK-inhibitor medications could be viable treatments for lichen planus—a condition for which there are currently no FDA-approved treatments.

These findings come from a paper published in Science Translational Medicine (Sept. 25, 2019; 11(511):eaav7561).

“We found the pathway behind the immune response that sparks lichen planus, which has a marked impact on quality of life,” said senior author Dr. Johann E. Gudjonsson, in a press release. Dr. Gudjonsson is an associate professor of dermatology at the University of Michigan (U-M) in Ann Arbor, Mich. He is also director of U-M’s new Skin Biology and Diseases Resource-based Center, funded by the U.S. National Institutes of Health.

“Clinically, lichen planus can resemble other autoimmune diseases in its manifestations, and we believe that lichen planus is likely also an autoimmune disease,” Dr. Gudjonsson said.

The researchers used a coculture model, using tissue samples from approximately 40 patients with an established diagnosis of lichen planus to identify the key inflammatory pathways involved. They found that the type II IFN, IFN-γ, primed keratinocytes and increased their susceptibility to CD8+ T cell–mediated cytotoxic responses through MHC class I induction. That process was in turn dependent on JAK2 and signal transducer and activator of transcription 1 (STAT1), but not JAK1 or STAT2 signalling.

“As there are existing treatments currently approved for arthritis that target this same [JAK2/STAT1] pathway, we provide some evidence in our skin model system that drugs targeting this pathway are likely to be effective in lichen planus,” said Dr. Gudjonsson.

“While our data suggests that JAK inhibitors would be effective in lichen planus, prospective randomized clinical trials are needed before we will know how effective and safe they would be in treating lichen planus.”

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