In recent research, scientists have found that the protein NF-kB c-Rel can worsen psoriasis symptoms when activated by the immune system’s signals. Gaining insights into how ‘c-Rel’ influences skin inflammation could pave the way for innovative treatments.
Psoriasis is an uncomfortable inflammatory skin disorder affecting millions around the globe, characterized by flare-ups triggered by immune cells that fight disease and infections.
Researchers at Case Western Reserve University School of Medicine have identified that the NF-kB c-Rel protein can exacerbate psoriasis symptoms once activated by signals from the immune system. They believe understanding the role of “c-Rel” in skin inflammation may lead to better treatment options.
The findings, recently published in eBioMedicine, focused on the role of c-Rel in immune cells known as dendritic cells (DCs). The study explored how c-Rel reacts to specific immunological signals from Toll Like Receptor 7 (TLR7), which is important for innate immunity and inflammation, thereby worsening psoriasis.
The absence of c-Rel was found to reduce inflammation responsible for the red, scaly patches on the skin.
“We think that targeting c-Rel and TLR7 could help scientists develop more focused treatments that lessen inflammation and improve psoriasis symptoms,” stated Parameswaran Ramakrishnan, an associate professor of pathology and the lead researcher at the study conducted at the Case Comprehensive Cancer Center and Louis Stokes Cleveland VA Medical Center. “This could potentially ease the suffering of millions living with skin inflammation.”
The researchers analyzed skin samples from individuals with psoriasis and utilized a mouse model displaying similar skin conditions. They assessed c-Rel levels and its activity in specially modified cells that lack the protein, as well as in the mouse model without c-Rel.
The aim was to gain a deeper understanding of c-Rel’s influence on the immune response in psoriasis.
“Our research indicates that c-Rel is crucial for psoriasis inflammation,” remarked Angela Liu, the lead author and a recent graduate from the School of Medicine’s pathology department. “We observed elevated levels of c-Rel in psoriasis patients; moreover, mice without c-Rel showed considerable protection against developing psoriasis and experienced reduced inflammation.”
Ramakrishnan noted that their study highlighted the potential involvement of TLR7 and c-Rel signaling in human psoriasis. Several viruses that activate TLR7, such as HIV, HPV, and HCV, are associated with the onset of psoriasis.
“This research calls for further studies on the TLR7-c-Rel-dependent molecular mechanisms regulating DC function, which might explain how viral activation of TLR7 contributes to the severity of psoriatic disease,” Ramakrishnan added. “Moreover, it would be enlightening to investigate the roles of c-Rel and TLR7 in other significant diseases linked to these proteins, such as systemic lupus erythematosus and diabetes-related wound healing.”
