PPARγ: a key orchestrator of epidermal barrier, immune responses, and lipid metabolism in atopic dermatitis pathogenesis and therapy

Atopic dermatitis (AD) is an immune-mediated inflammatory dermatosis characterized by epidermal barrier dysfunction, immune dysregulation, and cutaneous microbial dysbiosis. Existing therapeutic modalities for AD are limited in efficacy and durability, highlighting an unmet clinical need for novel, safe, and effective treatment strategies. Peroxisome proliferator-activated receptor gamma (PPARγ), a pivotal nuclear receptor involved in metabolic and inflammatory regulation, has emerged as a promising therapeutic target for AD. Its pleiotropic mechanisms encompass the restoration of stratum corneum integrity, modulation of aberrant immunoinflammatory signaling, normalization of cutaneous lipid metabolism, and regulation of the cutaneous microbiome and neuroimmune circuitry. This review comprehensively synthesizes the mechanistic evidence linking PPARγ to AD pathogenesis and critically appraises its potential as a novel therapeutic.