Neutrophil extracellular traps promote macrophage inflammation in psoriasis

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Ruolin Li , Yunjie Xiong , Linqiang Ma , Chuan Peng , Shuangxin Qi , Rufei Gao , Ping Wang , Fengzeng Li , Junlong Li , Qifu Li , Aijun Chen
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Abstract

Psoriasis is a chronic inflammatory skin disease connected with immune dysregulation. Macrophages are key inflammatory cells in psoriasis but the specific mechanism of their activation is not fully understood. Neutrophil extracellular traps (NETs) have been shown to regulate macrophage function. Here, we found that NET deposition was increased in psoriasis lesions. Peptidylarginine deaminase 4 (PAD4, a key enzyme for NET formation) deficiency attenuated skin lesions and inflammation in an imiquimod-induced psoriatic mouse model. Furthermore, the STING signaling pathway was markedly activated in psoriasis and abolished by PAD4 deficiency. PAD4-deficient mice treated with the STING agonist DMXAA exhibited more severe symptoms and inflammation than control mice. Mechanistically, the STING inhibitor C-176 inhibited NET-induced macrophage inflammation and further inhibited the proliferation of HaCaT cells. Our findings suggest an important role of NETs in the pathogenesis of psoriasis, and activation of macrophage STING/NF-κB signaling pathway might involve in NETs related psoriasis.

中性粒细胞胞外捕获物会促进银屑病巨噬细胞的炎症反应。
银屑病是一种与免疫失调有关的慢性炎症性皮肤病。巨噬细胞是银屑病的主要炎症细胞,但其活化的具体机制尚不完全清楚。研究表明,中性粒细胞胞外捕获物(NET)可调节巨噬细胞的功能。在这里,我们发现牛皮癣皮损中的NET沉积增加。在咪喹莫特诱导的银屑病小鼠模型中,肽基精氨酸脱氨酶4(PAD4,NET形成的关键酶)缺乏可减轻皮损和炎症。此外,STING 信号通路在银屑病中被明显激活,并因 PAD4 缺乏而消失。用 STING 激动剂 DMXAA 治疗 PAD4 缺乏的小鼠比对照组小鼠表现出更严重的症状和炎症。从机理上讲,STING抑制剂C-176抑制了NET诱导的巨噬细胞炎症,并进一步抑制了HaCaT细胞的增殖。我们的研究结果表明,NET在银屑病的发病机制中起着重要作用,巨噬细胞STING/NF-κB信号通路的激活可能与NET相关的银屑病有关。
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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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