2. Academic Validation
  3. PTPN2 alleviates psoriasis by targeting the STING-STAT3 axis and restoring autophagy: in vitro and in vivo evidence

PTPN2 alleviates psoriasis by targeting the STING-STAT3 axis and restoring autophagy: in vitro and in vivo evidence

  • Immunobiology. 2026 May;231(3):153174. doi: 10.1016/j.imbio.2026.153174.
Yingying Yang 1,  Yuanqiu Zhong 2,  Fanghua Liu 3,  Shougang Liu 4,  Yongfeng Chen 5
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province 230032, People's Republic of China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui Province 230032, People's Republic of China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui Province 230032, People's Republic of China; Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province 510091, People's Republic of China.
  • 2 Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province 510091, People's Republic of China.
  • 3 Department of Dermatology, Ganzhou Municipal Hospital, Ganzhou, Jiangxi Province 341000, People's Republic of China.
  • 4 Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province 510091, People's Republic of China. Electronic address: [email protected].
  • 5 Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province 230032, People's Republic of China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui Province 230032, People's Republic of China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui Province 230032, People's Republic of China; Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong Province 510091, People's Republic of China. Electronic address: [email protected].
PMID: 41895215 DOI: 10.1016/j.imbio.2026.153174
Abstract

Here, we investigated the role of protein tyrosine Phosphatase nonreceptor type 2 (PTPN2) in psoriasis pathogenesis, focusing on its regulation of the stimulator of interferon genes-signal transducer and activator of transcription 3 (STING-STAT3)-autophagy axis. Using cellular and imiquimod-induced mouse models, we assessed PTPN2 expression and function using multiple techniques, including immunofluorescence, co-immunoprecipitation, and Western blotting. A significant downregulation of PTPN2 expression was observed in psoriatic tissues. We established that PTPN2 directly interacts with STING and regulates its phosphorylation, with direct evidence from catalytic-dead PTPN2 mutant experiments showing that PTPN2's dephosphorylation of STING is activity-dependent. PTPN2 overexpression curbed keratinocyte proliferation, stimulated Apoptosis and Autophagy, and reduced the secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL) 23 subunit alpha (A), and IL-17A. The application of a STING agonist mitigated these effects, whereas STAT3 inhibition restored them. PTPN2 overexpression attenuated psoriatic pathology, and this therapeutic benefit was further enhanced by co-administering the Autophagy Inducer rapamycin. Collectively, our results delineate a novel mechanism by which PTPN2 alleviates psoriasis-like pathology in keratinocytes by targeting the STING-STAT3 pathway and promoting Autophagy and Apoptosis. These findings indicate that PTPN2 is a potential therapeutic target, with in vivo validation supporting its translational relevance.

Keywords

Apoptosis; Autophagy; PTPN2; Psoriasis; STAT3; STING.

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