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Qun Wang,* Jiangyan Wei,* Xin Wang,* Fang Yuan, Jingqing Sun Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, 100010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingqing Sun, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, 23 Meishuguan Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email sunjingqing@bjzhongyi.comBackground: Psoriasis is a common chronic inflammatory skin disease with unclear pathogenesis and limited treatment. Fire needling acupuncture is a distinctive acupuncture technique that involves the rapid insertion of red-hot needles into skin lesions or acupoints. It has been shown to exert anti-inflammatory and immunomodulatory effects and to effectively alleviate the clinical symptoms of psoriasis. This study aims to explore the underlying mechanisms of fire needling acupuncture in the treatment of psoriasis.Methods: Imiquimod was used to induce the psoriasis-like mouse model, and five groups were established: Control, Imiquimod (IMQ), IMQ + Methotrexate, IMQ + Fire needling acupuncture, and IMQ + Cl-amidine. Skin lesion severity and epidermal thickness were evaluated using the Psoriasis Area and Severity Index (PASI) and hematoxylin and eosin (H&E) staining. The levels of inflammatory cytokines (IL-23, IL-17, TNF-α, and IL-1β) in skin lesions were quantified by enzyme-linked immunosorbent assay (ELISA). The expression of epidermal proliferation and differentiation markers (Ki67 and K10), neutrophil surface marker (Ly6G), and neutrophil extracellular traps (NETs)-associated markers (MPO and Cit-H3) were evaluated by immunofluorescence and immunohistochemistry. In addition, the expression levels of TLR4, MyD88, NF-κB, p-NF-κB, and LCN2 in epidermis were quantified by Western blot analysis.Results: Fire needling acupuncture significantly reduced PASI scores, epidermal thickness, and the levels of IL-23, IL-17, TNF-α, and IL-1β in psoriasis-like lesions. It also decreased Ki67 expression while increasing K10 expression in the epidermis. Moreover, the expression of Ly6G, MPO, and Cit-H3 in the lesions was reduced, and the protein levels of TLR4, MyD88, p-NF-κB, and LCN2 were downregulated in the epidermis after fire needling acupuncture treatment. Comparable effects were observed with methotrexate and Cl-amidine.Conclusion: Fire needling acupuncture effectively improves skin lesions, suppresses abnormal keratinocyte proliferation and differentiation, and alleviates local inflammation in imiquimod-induced psoriasis-like mice. These therapeutic effects may be attributed to reduced neutrophil infiltration and NETs formation, as well as inhibition of TLR4/MyD88/NF-κB/LCN2 pathway.Keywords: fire needling acupuncture, psoriasis, neutrophil extracellular traps, NETs, toll-like receptor 4, TLR4, nuclear factor-kappa B, NF-κB, lipocalin-2, LCN2