GS-9620 alleviates psoriasis-like inflammation by regulating autophagy in keratinocytes

Abstract

Background: Psoriasis is an immune-driven dermatosis marked by keratinocyte hyperproliferation. GS-9620, a TLR7 agonist, previously mitigated EV71-triggered inflammation in mice; here we probe its anti-psoriatic potential and mechanisms.

Methods: IMQ-induced psoriasis-like mice were treated with GS-9620 or MTX; severity was tracked by PASI and histology. Skin/spleen cytokines (IL-1β, IL-6, IL-18, HMGB1, TNF-α) were quantified via ELISA; immune subsets were quantified by flow cytometry. Autophagy proteins (ATG5/12/16 L1) and NLRP3 were assessed by IHC/Western blot. In vitro, M5-stimulated primary keratinocytes were treated with GS-9620 ± autophagy modulators, followed by cytokine and protein analyses.

Results: GS-9620 markedly reduced erythema, scaling and epidermal thickness, lowered skin and systemic cytokines, and decreased splenic CD3⁺/CD4⁺IL-17A⁺ cells. It restored ATG5/12/16 L1 expression while suppressing NLRP3 both in lesions and in M5-stimulated keratinocytes, leading to diminished IL-1β, IL-6, IL-18, HMGB1 and TNF-α release.

Conclusions: GS-9620 alleviates psoriasis by enhancing autophagy and dampening NLRP3-mediated inflammation, offering a promising therapeutic avenue.

Keywords

anti-psoriasis drugs / autophagy / GS-9620 / NLRP3 / PASI / psoriasis

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2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.