Fatty acid–related immune network in psoriasis: metabolic regulation of innate and adaptive immunity

Psoriasis is a chronic inflammatory skin disorder driven by dysregulation of the Treg/Th17 axis, where enhanced Th17 activity promotes keratinocyte proliferation and inflammation, while impaired Treg function exacerbates immune dysregulation. Emerging evidence highlights peroxisome proliferator-activated receptor γ (PPARγ) as a key regulator of fatty acid oxidation (FAO), a metabolic pathway critical for Treg differentiation and function. PPARγ activation enhances FAO via upregulation of CD36, CPT1, and AMPK signaling, while suppressing glycolysis, thereby skewing the Treg/Th17 balance toward immune tolerance. Concurrently, short-chain fatty acids (SCFAs), microbial metabolites with immunomodulatory properties. ameliorate psoriatic inflammation by promoting Treg expansion, inhibiting Th17 polarization, and modulating innate immune cells (neutrophils, dendritic cells, and macrophages). SCFAs exert their effects through receptor-dependent signaling and epigenetic mechanisms (HDAC inhibition), while derivative compounds and probiotic interventions enhance therapeutic potential. This review summarizes mechanistic insights into PPARγ-driven FAO and SCFA-mediated immunomodulation, proposing novel metabolic and microbiome-targeted strategies for psoriasis treatment.