Biological agent exerts therapeutic effects by reversing abnormalities in amino acid metabolic pathways in psoriasis

Abstract Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis involving immune system dysregulation and inflammation. Previous studies have indicated that metabolic abnormalities are closely related to the development and occurrence of psoriasis. However, the specific involvement of amino acid metabolism in the pathogenesis of psoriasis remains unclear. In this study, we conducted a comprehensive analysis of amino acid metabolism pathway changes in psoriasis patients using transcriptome data, genome‐wide association studies (GWASs) data, and single‐cell data. Our findings revealed 11 significant alterations in amino acid metabolism pathways within psoriatic lesions, with notable restorative changes observed after biological therapy. Branched‐chain amino acids, tyrosine and arginine metabolism have a causal relationship with the occurrence of psoriasis and may play a crucial role by promoting the proliferation and differentiation of the keratinocytes or immune‐related pathways. Activation of phenylalanine, tyrosine and tryptophan biosynthesis suggests a favourable prognosis of psoriasis after treatment. Additionally, we identified the abnormal metabolic pathways in specific cell types and key gene sets that contribute to amino acid metabolic disorders in psoriasis. Overall, our study enhances understanding of the role of metabolism in the pathogenesis of psoriasis and provides potential targets for developing new therapeutic strategies for the disease.