Phenylalanine exacerbates psoriasiform inflammation through NF‑κB‑mediated dendritic cell activation and Th17...

Metabolic dysregulation has been increasingly recognized as a key driver in the pathogenesis of psoriasis; however, the specific mechanistic contributions of amino acid perturbations remain poorly understood. The present study, through comprehensive metabolomic profiling, observed a marked accumulation of phenylalanine in both the circulation and skin lesions of psoriatic mice. Notably, a high‑phenylalanine diet exacerbated psoriasiform skin inflammation of imiquimod‑induced psoriasis, whereas dietary restriction of phenylalanine or administration of L‑type amino acid transporter inhibitors effectively alleviated skin inflammation. Mechanistically, transcriptome sequencing of dendritic cells identified phenylalanine as a potent metabolic trigger. The present analysis revealed that high phenylalanine levels alone significantly elevated the baseline expression of notable pro‑inflammatory cytokines and this inflammatory response was further amplified in the presence of imiquimod. The present study determined that this pro‑inflammatory effect was mediated through the NF‑κB signaling pathway, which subsequently promoted the differentiation of T helper 17 cells. Collectively, the present findings uncovered a previously unrecognized metabolic checkpoint in psoriasis and suggested that restriction of phenylalanine represents a promising, non‑toxic adjunctive therapeutic strategy for the clinical management of psoriasis.