
Researchers at Case Western Reserve University School of Medicine in Cleveland have identified a key protein that may exacerbate symptoms of psoriasis. The study, published in eBioMedicine, reveals how the protein NF-kB c-Rel intensifies skin inflammation when activated by immune system signals.
The research team, led by Parameswaran Ramakrishnan, PhD, associate professor of pathology and member of the Case Comprehensive Cancer Center, focused on the interaction between c-Rel and dendritic cells (DCs). They discovered that c-Rel responds to specific immunological signals through Toll Like Receptor 7 (TLR7), which regulates innate immunity and inflammation.
"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," Dr. Ramakrishnan said in a press release. "This may help relieve the discomfort of millions of people [who] live with skin inflammation."
The study examined skin samples from psoriasis patients and utilized a mouse model with similar skin changes. Researchers analyzed c-Rel levels and their behaviour in specially engineered cells lacking the protein, as well as in mice lacking c-Rel.
Angela Liu, lead author and recent graduate of the School of Medicine's pathology department, noted, "Our research shows that c-Rel plays a major role in psoriasis inflammation. We saw higher levels of c-Rel in psoriasis; mice lacking c-Rel were significantly protected from developing psoriasis and showed less inflammation."
The findings suggest a potential link between viral activation of TLR7 and the worsening of psoriatic disease. Several viruses known to activate TLR7, including HIV, HPV, and HCV, have been associated with the development of psoriasis.
Dr. Ramakrishnan emphasized the need for further research, stating, "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."
The authors believe the study's implications extend beyond psoriasis, potentially offering insights into other conditions involving c-Rel and TLR7, such as systemic lupus erythematosus and wound healing in diabetes.
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