Psoriasis is a chronic autoimmune skin disease that speeds up the growth cycle of skin cells. It is the most common autoimmune disease in the United States, with an estimated 7.5 million Americans who suffer from the condition. It affects approximately 125 million people globally, which is about 2.2% of the worldwide population. The severity of psoriasis symptoms can vary significantly between different patients; however, for the majority of patients, it presents a large problem for their everyday life. Now, a new mouse model study by researchers at Michigan Medicine demonstrates that targeting a skin protein may reduce the severity of psoriasis.
Their findings are published in the Journal of Investigative Dermatology, in a paper titled, “Interferon Kappa Is a Rheostat for Development of Psoriasiform Inflammation.” Their findings suggest using therapies to regulate interferon states may limit inflammation in psoriasis.
The researchers discovered in their mouse model that changing the levels of interferon kappa altered the severity of inflammation and production of cytokines. Their mouse model revealed that when more interferon kappa was present, more psoriasis inflammation was present. Decreasing interferon kappa levels reduced disease.
“Psoriasis is a common, inflammatory autoimmune skin disease,” wrote the researchers. “Early detection of a type I interferon (IFN) signature occurs in many psoriasis lesions, but the source of IFN production remains debated. Interferon kappa (IFN-κ) is an important source of type I IFN production in the epidermis. We identified a correlation between IFN–regulated and psoriasis-associated genes in human lesional skin.”
“We’ve known that psoriatic inflammation is marked by interferon-related gene expression, but how interferons alter the severity of the disease has not been clear,” explained J. Michelle Kahlenberg, MD, PhD, associate professor of rheumatology at Michigan Medicine and senior author of the paper. “Understanding how interferon kappa may modulate psoriasis brings us one step closer to optimizing our treatments.”
“Three mouse strains at 10 weeks of age were used: wild type (WT) C57Bl/6, C57Bl/6 that overexpress Ifnk in the epidermis (TG), and total body Ifnk-/- (KO). Psoriasis was induced by topical application of IMQ on both ears for eight consecutive days. Notably, the severity of skin lesions and inflammatory cell infiltration was significantly increased in TG>WT>KO mice,” the researchers wrote.
The overexpressed protein alone didn’t induce the disease, but it primed the skin for the inflammatory response that followed.
“This work shows how the context of the skin environment can shape inflammatory responses,” said Mehrnaz Gharaee-Kermani, PhD, lead author of the study and a senior research lab specialist at Michigan Medicine. “It will be exciting to see how this can be applied in clinic.”
The researchers are conducting further studies to under interferon kappa’s role in posoriasis. The researchers are working on a Taubman Institute-sponsored study at Michigan Medicine and in partnership with Johann E. Gudhonsson, MD, PhD, receiving funding through the National Psoriasis Foundation.
Coupled with the study’s findings, personalized medicine will be paramount as physicians attempt to treat this disease, Kahlenberg said.
“Until now, treatments have been tested by studying a drug in hundreds of patients, lumping the average of them all together and targeting the average of those patients,” Kahlenberg said. “As any patient who has been on these medications will tell you, this trial–and-error approach wastes patient time and money trying to get control of the disease. Understanding a patient’s background level of interferon might help us target things within that person to make their disease better faster and stay in remission.”
