Immunometabolic Dysregulation in Psoriasis: Mechanisms Driving Inflammation and Emerging Therapeutic Targets

Psoriasis is increasingly recognized as a systemic immuno-metabolic disorder in which chronic inflammation interacts with alterations in cellular energy metabolism.

To summarize current evidence on immunometabolic dysregulation in psoriasis and highlight emerging metabolic-targeted therapeutic strategies.

A narrative review of recent literature examining metabolic pathways, immune responses, and therapeutic interventions involved in psoriasis pathogenesis was conducted.

Psoriatic keratinocytes, T cells, dendritic cells, and macrophages undergo significant metabolic reprogramming characterized by increased glycolysis, altered lipid metabolism, mitochondrial dysfunction, and excessive reactive oxygen species production. These metabolic disturbances contribute to keratinocyte hyperproliferation and sustain Th17-driven inflammation, linking skin pathology with systemic comorbidities such as obesity, insulin resistance, dyslipidaemia, and endothelial dysfunction. Key nutrient-sensing regulators, including mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), hypoxia-inducible factor-1α (HIF-1α), sirtuin-1 (SIRT1), and PGC-1α, integrate metabolic status with inflammatory signaling. Additionally, adipokine imbalance and metabolic stress promote chronic metaflammation.

Targeting immunometabolic pathways through glycolysis inhibitors, AMPK activators, mTOR modulators, mitochondrial-targeted antioxidants, and lipid-regulating agents may restore metabolic homeostasis and reduce inflammation. Advances in multi-omics approaches may further facilitate biomarker discovery and precision-based therapeutic strategies in psoriasis management.