Researchers at Case Western Reserve University School of Medicine have discovered that the protein NF-kB c-Rel plays a significant role in intensifying psoriasis symptoms when activated by immune system signals.
Published in eBioMedicine, the study investigates the contribution of c-Rel to the function of dendritic cells (DCs), a type of immune cell central to the development of psoriasis. Specifically, the research explores how c-Rel responds to signals from toll-like receptor 7 (TLR7), a protein involved in regulating innate immunity and inflammation. These processes are crucial in the worsening of psoriasis.
Principal investigator Parameswaran Ramakrishnan, associate professor of pathology at Case Western and a researcher at the Louis Stokes Cleveland VA Medical Center, believes that targeting c-Rel and TLR7 could lead to more precise treatments aimed at reducing inflammation and alleviating psoriasis symptoms. “Focusing on these proteins could offer a pathway to relief for the millions affected by skin inflammation,” he said in a press release.
Psoriasis is a chronic, immune-related condition that causes skin inflammation, resulting in patches that itch, burn, and sting. It affects around 8 million people in the United States, with approximately 30% of those individuals also experiencing psoriatic arthritis, which causes joint pain and swelling. The disease places a substantial economic burden on healthcare, as individuals with psoriasis often require more medical resources than those without the condition.
While previous studies have suggested the involvement of the Rel gene in psoriasis, the exact mechanisms remain unclear. This latest study from Case Western provides new insights into how c-Rel contributes to the disease.
Focusing on dendritic cells—key mediators of psoriasis—researchers observed that these cells produce inflammatory markers and activate T cells. They also examined the role of toll-like receptors, which are essential proteins in the immune system and are present on various immune and non-immune cells. c-Rel is known to be a critical component of several toll-like receptor pathways.
To study the protein’s impact, the team analyzed skin samples from psoriasis patients and examined a mouse model with similar skin conditions. The researchers measured c-Rel levels and observed its effects in specially engineered cells without the protein. They also studied a mouse model lacking c-Rel entirely.
The results showed that the absence of c-Rel significantly reduced inflammation and the characteristic red, scaly skin patches associated with psoriasis. “Mice without c-Rel were substantially protected from developing psoriasis and displayed much less inflammation,” said Angela Liu, lead author and recent graduate of the School of Medicine’s pathology department.
Ramakrishnan emphasized the potential of targeting c-Rel and TLR7 signaling pathways as part of future psoriasis treatments. He noted that various viruses—such as HIV, human papillomavirus (HPV), and hepatitis C virus (HCV)—that activate TLR7 are linked to psoriasis development.
The findings suggest that further exploration of c-Rel’s role in skin inflammation could lead to novel therapies. “Our research underscores the importance of understanding the TLR7-c-Rel signaling pathway, which may also have broader implications for diseases such as lupus and wound healing in diabetes,” Ramakrishnan concluded.
The study opens the door for new approaches in treating psoriasis and highlights the need for continued research into immune system regulation.
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