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

  • Animal Model Exp Med. 2026 Jun 9. doi: 10.1002/ame2.70222.
Yansi Lyu  1 ,  Wei Zhou  2 ,  Pei Zhang  3 ,  Chen Lin  2 ,  Xin Wen  2 ,  Zigang Zhao  4 ,  Guoqiang Zhang  5 ,  Qian Zhang  6 ,  Si Chen  2
Affiliations
  • 1. Department of Dermatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, P. R. China.
  • 2. Department of Immunology, Shenzhen University Medical School, Shenzhen, Guangdong, P. R. China.
  • 3. Department of Pathology, Affiliated Hospital of Hebei University, Baoding, Hebei, P. R. China.
  • 4. Department of Dermatology, Hainan Hospital of PLA General Hospital, Sanya, Hainan, P. R. China.
  • 5. Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China.
  • 6. Department of Dermatology, Shenzhen Nanshan People's Hospital, Shenzhen, Guangdong, P. R. China.
PMID: 42265830 DOI: 10.1002/ame2.70222
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
GS‐9620; NLRP3; PASI; anti‐psoriasis drugs; autophagy; psoriasis.
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