S1PR3-driven positive feedback loop sustains STAT3 activation and keratinocyte hyperproliferation in psoriasis.

ABSTRACT: Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and persistent inflammation. Although persistent activation of signal transducer and activator of transcription 3 (STAT3) is implicated in its pathogenesis, the mechanisms underlying the sustained STAT3 activation remain poorly understood. Here, we identify sphingosine-1-phosphate receptor 3 (S1PR3) as a critical regulator of STAT3 activation and psoriasis pathogenesis, orchestrating a self-amplifying circuit that sustains keratinocyte hyperproliferation and chronic inflammation. S1PR3 expression is markedly elevated in psoriatic lesions and correlates with disease severity. Using genetic and pharmacological approaches, we reveal a novel S1PR3-Src-STAT3 signaling axis that drives both ear

SUBMITTER: Lian P 

PROVIDER: S-EPMC11746942 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature