The multifaceted role of NF-κB signaling in psoriasis: from inflammatory amplification to epidermal remodeling.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by persistent epidermal hyperplasia and relapsing inflammation. Although extensive progress has been made in elucidating individual pathogenic pathways, a unifying framework that integrates innate immune activation, adaptive immune maintenance, and keratinocyte-driven amplification remains incomplete. Accumulating evidence indicates that nuclear factor-κB (NF-κB) functions as a central convergence hub that coordinates these diverse inflammatory inputs in psoriasis. In this review, we synthesize recent advances demonstrating how innate immune sensors, including nucleic acid-sensing pathways and Toll-like receptors, converge on NF-κB to initiate inflammatory programs, and how adaptive immune circuits-particularly Th17/IL-17 signaling-exploit NF-κB to sustain disease chronicity. We further highlight the active role of keratinocytes as intrinsic amplifiers of inflammation through NF-κB-dependent programs governing hyperproliferation, oxidative stress responses, and secondary cytokine production. Beyond canonical signaling, emerging evidence reveals that non-coding RNAs and epigenetic regulators fine-tune NF-κB activity, shaping transcriptional persistence and inflammatory memory in psoriatic skin. Finally, we discuss therapeutic strategies targeting the NF-κB convergence hub, including upstream sensor antagonism, adaptor-level modulation, multi-target small molecules, natural products, and advanced skin-targeted delivery systems. By framing NF-κB as a networked regulatory hub rather than a linear pathway, this review provides an integrated perspective on psoriasis pathogenesis and highlights opportunities for precision immunomodulation with improved efficacy and safety.