TXNRD1的药理学抑制通过抑制角质形成细胞增殖和NF-κB信号传导减轻银屑病样皮炎
Pharmacological inhibition of TXNRD1 attenuates psoriasis-like dermatitis by suppressing keratinocyte proliferation and NF-κB signaling.
摘要(中文译文)
银屑病是一种以角质形成细胞过度增殖和免疫激活为特征的慢性炎症性皮肤病。硫氧还蛋白还原酶1（TXNRD1）是硫氧还蛋白抗氧化系统的关键酶，调控细胞氧化还原平衡和炎症信号传导；然而，其在银屑病中的功能作用尚不清楚。本研究中，我们证实TXNRD1在银屑病患者皮损组织及咪喹莫特诱导的小鼠银屑病样皮炎中表达显著上调。在体外实验中，角质形成细胞中TXNRD1的基因缺失显著抑制了细胞增殖，减少了促炎细胞因子的产生，并降低了对CD4 T细胞的趋化活性。重要的是，局部给予TXNRD1抑制剂TRi在体内显著减轻了银屑病样皮肤炎症，表现为表皮增生减少和CD4 T细胞浸润减少。机制上，TNF-α和IFN-γ诱导角质形成细胞中TXNRD1的表达并激活NF-κB信号通路。TXNRD1缺失显著减弱了TNF-α/IFN-γ诱导的NF-κB磷酸化，导致趋化因子表达减少和T细胞募集受损。这些发现表明TXNRD1是角质形成细胞驱动炎症反应的关键调控因子，并提供药理学证据支持TXNRD1作为银屑病的潜在治疗靶点。
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation and immune activation. Thioredoxin reductase 1 (TXNRD1), a key enzyme of the thioredoxin antioxidant system, regulates cellular redox balance and inflammatory signaling; however, its functional role in psoriasis remains unclear. Here, we demonstrate that TXNRD1 expression is markedly upregulated in lesional skin from psoriasis patients and in imiquimod-induced psoriasis-like dermatitis in mice. Genetic deletion of TXNRD1 in keratinocytes significantly suppressed cell proliferation, reduced pro-inflammatory cytokine production, and diminished chemotactic activity toward CD4 T cells in vitro. Importantly, topical administration of the TXNRD1 inhibitor TRi markedly alleviated psoriasis-like skin inflammation in vivo, as evidenced by reduced epidermal hyperplasia and decreased CD4 T cell infiltration. Mechanistically, TNF-α and IFN-γ induced TXNRD1 expression and activated NF-κB signaling in keratinocytes. TXNRD1 deficiency significantly attenuated TNF-α/IFN-γ-induced NF-κB phosphorylation, leading to reduced chemokine expression and impaired T-cell recruitment. These findings identify TXNRD1 as a critical regulator of keratinocyte-driven inflammatory responses and provide pharmacological evidence supporting TXNRD1 as a potential therapeutic target for psoriasis.
如何引用
AMA
Xiao Zhou, Siying Li, Xin Luo, Yanshan Zhu, Yi Jin, Shuhan Yang, et al. Pharmacological inhibition of TXNRD1 attenuates psoriasis-like dermatitis by suppressing keratinocyte proliferation and NF-κB signaling.. International immunopharmacology. 2026; doi:10.1016/j.intimp.2026.116936.
APA
Xiao Zhou, Siying Li, Xin Luo, Yanshan Zhu, Yi Jin, Shuhan Yang, et al (2026). Pharmacological inhibition of TXNRD1 attenuates psoriasis-like dermatitis by suppressing keratinocyte proliferation and NF-κB signaling.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116936
GB/T 7714
Xiao Zhou, Siying Li, Xin Luo, Yanshan Zhu, Yi Jin, Shuhan Yang, et al. Pharmacological inhibition of TXNRD1 attenuates psoriasis-like dermatitis by suppressing keratinocyte proliferation and NF-κB signaling.[J]. International immunopharmacology, 2026 doi:10.1016/j.intimp.2026.116936.
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