Divergent immunometabolic reprogramming in psoriasis and atopic dermatitis: a tale of two inflammatory skin diseases

Psoriasis (PSO) and atopic dermatitis (AD) are the two most common chronic inflammatory skin diseases in clinical practice. For a long time, they have been classified in pathological immunology under the opposing model of "Th17/IL-17 vs. Th2/IL-4-IL-13." However, over the past decade, with the rise of immunometabolism, our understanding of chronic inflammatory diseases has undergone a significant shift. Metabolic pathways in immune cells are no longer viewed merely as auxiliary systems providing energy, but rather as core regulatory networks that determine cellular differentiation and effector functions. In psoriasis, hallmark features include upregulation of glycolysis, activation of hypoxia-inducible factor-1α (HIF-1α), abnormalities in cholesterol metabolism, and Warburg-like metabolism in keratinocytes. In AD, defects in epidermal ceramide synthesis, impaired essential fatty acid metabolism, disruption of the tryptophan-kynurenine pathway, and abnormal aromatics receptor (AhR) signaling constitute its unique metabolic profile. This article systematically reviews the distinct pathways of metabolic reprogramming in keratinocytes and immune cells in psoriasis and AD, and summarizes the mechanisms of action of key molecules such as mTOR and AMPK. Furthermore, it explores the differential therapeutic potential of metabolism-targeted drugs, including metformin, statins, PPARγ agonists, and AhR modulators. Furthermore, the expression of common regulatory factors such as HIF-1α, PPARγ, and SREBP exhibits opposite trends in the two diseases. Finally, the article discusses the differential therapeutic potential of these metabolite-targeted drugs. This paper compares psoriasis and AD within a unified metabolic immunology framework, aiming to elucidate how these two diseases evolve from similar inflammatory responses into conditions with distinctly different clinical manifestations, and to provide a new theoretical foundation for future metabolism-based personalized therapies.