PTPN2 inhibits the proliferation of psoriatic keratinocytes by dephosphorylation of STAT3

Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models. PTPN2 and signal transducer and activator of transcription 3 (STAT3) were overexpressed or silenced in human keratinocytes or an interleukin (IL)-6-induced psoriasis HaCaT cell model using overexpression plasmid transfection or small interfering RNA technology in vitro, and the effects of PTPN2 on STAT3, HaCaT cell function, and autophagy levels were investigated using reverse transcription-quantitative polymerase chain reaction, Western blot, Cell Counting Kit 8, 5-ethynyl-20-deoxyuridine, flow cytometry, and transmission electron microscopy. PTPN2 expression was found to be significantly downregulated in psoriatic tissues. Then, the in vitro antipsoriatic properties of PTPN2 were investigated in an IL-6-induced psoriasis-like cell model, and the results demonstrated that inhibition of keratinocyte proliferation by PTPN2 may be associated with elevated STAT3 dephosphorylation and autophagy levels. These findings provide novel insights into the mechanisms of autophagy in psoriatic keratinocytes and may be essential for developing new therapeutic strategies to improve inflammatory homeostasis in psoriatic patients. Psoriasis is a recurrent and chronic systemic inflammatory skin disease, which seriously affects the physical and mental health of patients. In this manuscript, we report for the first time that protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is significantly underexpressed in psoriasis. PTPN2 mediates signal transducer and activator of transcription 3 dephosphorylation, promoting autophagy levels and inhibiting keratinocyte proliferation. To the best of our knowledge, psoriasis cannot be adequately controlled even though the clinical efficacy of the present treatment for the etiology of the condition has greatly improved. The search explores the mechanism of pathogenesis of PTPN2 in psoriasis, providing new insights into the mechanism of autophagy in psoriatic keratinocytes, and may have important implications for the development of new therapeutic strategies to improve inflammatory homeostasis in patients with psoriasis.