Research Identifies Role of Key Protein in Psoriasis

Researchers at Case Western Reserve University School of Medicine have determined that a protein called NF-kB c-Rel can intensify the symptoms of psoriasis when activated by signals from the body’s immune system.

The study, published recently in eBioMedicine, examined how c-Rel contributes to the function of a type of immune cell known as dendritic cells (DCs). The study examined how c-Rel responds to specific immunological signals through toll like receptor 7 (TLR7), which regulates innate immunity and inflammation and exacerbates psoriasis.

Parameswaran Ramakrishnan

“We believe that by focusing on c-Rel and TLR7, scientists might be able to create more targeted treatments that reduce inflammation and help psoriasis symptoms,” Parameswaran Ramakrishnan, associate professor of pathology, member of the Case Comprehensive Cancer Center and researcher at Louis Stokes Cleveland VA Medical Center, the study’s principal investigator, said in a news release. “This may help relieve the discomfort millions of people live with skin inflammation.

Psoriasis is a chronic, immune-related disease that leads to inflammation of the skin, leading to patches that itch, burn and sting. About 8 million people in the United States have psoriasis. About 30% of people with psoriasis also have psoriatic arthritis, which leads to joint pain, stiffness and swelling. The economic burden of psoriasis is substantial, and those with psoriasis used higher healthcare resources than those without psoriasis, according to one study from 2018.

Previous studies have suggested the Rel gene is implicated in psoriasis, including this one published in 2016, but the mechanism is not fully understood, researchers from Case Western said.

In the Case Western study, researchers focused on dendritic cells (DCs), which are key cell mediators in psoriasis, and they produce inflammatory mediators and T cell activation. Researchers also looked at a specific toll-like receptor, which are proteins that play a key role in the immune system. Toll-like receptors are expressed on a variety of immune and nonimmune cells. c-Rel has been shown to be a critical component of various toll-like receptor pathways.

The Case Western researchers examined skin samples from psoriasis patients and a mouse model with similar skin changes. They analyzed c-Rel levels and its behavior in specially engineered cells lacking the protein; they also examined the mouse model lacking c-Rel.

The researchers also found the absence of c-Rel alleviates inflammation that causes red, scaly patches on the skin. “Mice lacking c-Rel were significantly protected from developing psoriasis and showed less inflammation,” Angela Liu, lead author and a recent graduate of the School of Medicine’s pathology department, said in the press release.

Ramakrishnan said their study revealed the potential role for TLR7 and c-Rel signaling in human psoriasis. A range of viruses that activate TLR7, including human immunodeficiency virus (HIV), human papilloma virus (HPV) and hepatitis C virus (HCV), are linked to the development of psoriasis.

Understanding how “c-Rel” affects skin inflammation could lead to new treatments, researchers said.

“The research warrants future studies on TLR7-c-Rel-dependent molecular mechanism regulating DC function as a potential link for how viral TLR7 activation is involved in worsening psoriatic disease,” Ramakrishnan said. “From a broad perspective, it would be interesting to further explore the role of c-Rel and TLR7 in other biologically relevant diseases involving these proteins, such as systemic lupus erythematosus and wound healing in diabetes.”