practicaldermatology.com
Targeting signaling that is dependent on nuclear factor kappa B (NF-κB) c-Rel could effectively dampen excessive inflammation in TLR7-related skin inflammation, according to new research from Case Western Reserve University published in eBioMedicine.
While c-Rel is a psoriasis susceptibility locus, mechanisms underlying its transactivation during disease were not well understood, the authors noted in “NF-κB c-Rel is a critical regulator of TLR7-induced inflammation in psoriasis.”
“Inflammation in psoriasis can be triggered following Toll-like Receptor 7 (TLR7) signaling in dendritic cells (DCs), and c-Rel is a critical regulator of DC function,” they wrote. “Here, we studied the mechanism of TLR7-induced c-Rel-mediated inflammation in DCs.”
The researchers analyzed the overall expression in skin sections from psoriasis patients in human transcriptomics data sets and the imiquimod-induced psoriasis mouse model. They found that c-Rel is highly expressed in lesional skin of patients with psoriasis and TLR7-induced psoriatic lesions in mice.
“c-Rel deficiency protected mice from the disease, and specifically compromised TLR7-induced, and not TLR9- or TLR3-induced, inflammation in dendritic cells,” they wrote. “Mechanistically, c-Rel deficiency disrupted activating NF-κB dimers and allowed binding of inhibitory NF-κB homodimers to the IL-1β and IL-6 promoters thus inhibiting their expression. This functionally compromises the ability of c-Rel deficient DCs to induce Th17 polarisation, which is critical in psoriasis pathogenesis.”