Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model
Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model
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银屑病炎症通过IL-23/STAT 3信号通路增强小鼠过敏性气道炎症
DOI：
10.1016/j.bcp.2016.10.012
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发表时间：
2017-01-15
影响因子：
5.8
通讯作者：
Ahmad, Sheikh F.
中科院分区：
文献类型：
--
作者：
Nadeem, Ahmed;Al-Harbi, Naif O.;Ahmad, Sheikh F.
银屑病是一种以IL-23/STAT 3/Th 17轴激活为特征的自身免疫性炎症性皮肤病。最近，银屑病炎症已被证明与哮喘有关。然而，以前没有研究探讨银屑病炎症如何影响气道炎症。因此，本研究在小鼠模型中研究咪喹莫特（IMQ）诱导的银屑病炎症对蟑螂提取物（CE）诱导的气道炎症的影响。对小鼠进行局部和鼻内施用IMQ和CE以分别发展银屑病和气道炎症。在肺/脾中进行与炎症、Th 17/Th 2/Th 1细胞免疫应答及其特征性细胞因子/转录因子相关的各种分析。过敏小鼠的银屑病炎症与气道炎症增加以及Th 2/Th 17细胞/特征细胞因子/转录因子的同时增加有关。银屑病小鼠脾脏CD 4 + T细胞和CD 11 c+树突状细胞STAT 3/RORC和IL-23 mRNA表达分别增加。这使我们探索全身性IL-23/STAT 3信号传导对气道炎症的影响。局部应用STA-21（一种小分子STAT 3抑制剂）显著降低了患有银屑病炎症的过敏性小鼠的气道炎症。另一方面，将IL-23处理的脾CD 4 + T细胞从过敏小鼠过继转移到未处理的受体小鼠中，产生与具有银屑病炎症的过敏小鼠相似的混合嗜酸性粒细胞/嗜酸性粒细胞气道炎症。我们的数据表明，系统性IL-23/STAT 3轴是负责增强气道炎症在银屑病。目前的研究还表明，仅抗哮喘治疗可能不足以减轻银屑病哮喘患者的气道炎症负担。(C)2016 Elsevier Inc. All rights reserved.
Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively. Various analyses in lung/spleen related to inflammation, Th17/Th2/Th1 cell immune responses, and their signature cytokines/transcription factors were carried out. Psoriatic inflammation in allergic mice was associated with increased airway inflammation with concurrent increase in Th2/Th17 cells/signature cytokines/transcription factors. Splenic CD4+ T and CD11c+ dendritic cells in psoriatic mice had increased STAT3/RORC and IL-23 mRNA expression respectively. This led us to explore the effect of systemic IL-23/STAT3 signaling on airway inflammation. Topical application of STA-21, a small molecule STAT3 inhibitor significantly reduced airway inflammation in allergic mice having psoriatic inflammation. On the other hand, adoptive transfer of IL-23-treated splenic CD4+ T cells from allergic mice into naive recipient mice produced mixed neutrophilic/eosinophilic airway inflammation similar to allergic mice with psoriatic inflammation. Our data suggest that systemic IL-23/STAT3 axis is responsible for enhanced airway inflammation during psoriasis. The current study also suggests that only anti-asthma therapy may not be sufficient to alleviate airway inflammatory burden in asthmatics with psoriasis. (C) 2016 Elsevier Inc. All rights reserved.