sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells.
sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells.
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sRAGE 通过阻断气道树突状细胞中的 HMGB1/RAGE 信号传导来缓解中性粒细胞性哮喘
DOI：
10.1038/s41598-017-14667-4
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发表时间：
2017-10-27
影响因子：
4.6
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Zhang F;Su X;Huang G;Xin XF;Cao EH;Shi Y;Song Y
晚期糖基化终产物（RAGE）的受体在炎症反应中起作用。愤怒（Srage）的可溶形式充当诱饵，可以抑制愤怒与高级糖基化最终产物的相互作用，例如高迁移率组1（HMGB1）。我们已经证明，HMGB1在先前的研究中通过调节树突细胞（DC）功能来指导Th17偏斜。然而，HMGB1阻断随SRAGE的保护作用在中性粒细胞性哮喘的发展中尚不清楚。在这里，我们表明过敏原挑战在嗜中性粒细胞性哮喘的鼠模型中降低了Srage的表达，与中性粒细胞计数和白介素（IL）-17生产良好相关。当HMGB1信号在致敏之前通过气管内施用阻塞时，HMGB1表达，中性粒细胞炎症和Th17型反应显着降低。通过在气道CD11C+抗原呈递细胞中抑制RAGE和IL-23表达来实现SRAGE的抗哮喘作用。最后，我们表明SRAGE抑制了由重组HMGB1（RHMGB1）激活的树突状细胞（DCS）在体外抑制TH17极化。 RHMGB1激活的DC的过继转移足以恢复气道炎症，而RHMGB1加上SRAGE激活的DC的转移显着降低了嗜中性粒细胞炎症。因此，SRAGE可防止Th17介导的中性粒细胞性哮喘中的气道炎症，至少部分通过阻断DC中的HMGB1/RAGE信号传导。
Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE with advanced glycation end products such as High mobility group box 1 (HMGB1). We have demonstrated that HMGB1 directs Th17 skewing by regulating dendritic cell (DC) functions in a previous study. However, the protective effects of HMGB1 blockade with sRAGE in the development of neutrophilic asthma remain unclear. Here, we showed that allergen challenge decreased expression of sRAGE in a murine model of neutrophilic asthma, correlating well with neutrophil counts and interleukin (IL)-17 production. When HMGB1 signalling was blocked by intratracheal administration of sRAGE before sensitisation, HMGB1 expression, neutrophilic inflammation, and Th17-type responses were reduced significantly. Anti-asthma effects of sRAGE were achieved by inhibition of RAGE and IL-23 expression in airway CD11c+ antigen-presenting cells. Finally, we showed that sRAGE inhibited Th17 polarisation induced by recombinant HMGB1 (rHMGB1)-activated dendritic cells (DCs) in vitro. Adoptive transfer of rHMGB1-activated DCs was sufficient to restore airway inflammation, whereas transfer of rHMGB1 plus sRAGE-activated DCs significantly reduced neutrophilic inflammation. Thus, sRAGE prevents Th17-mediated airway inflammation in neutrophilic asthma at least partly by blocking HMGB1/RAGE signalling in DCs.
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影响因子：
3.1
作者：
通讯作者：
--
影响因子：
4.3
作者：
Ebina M;Taniguchi H;Miyasho T;Yamada S;Shibata N;Ohta H;Hisata S;Ohkouchi S;Tamada T;Nishimura H;Ishizaka A;Maruyama I;Okada Y;Takashi K;Nukiwa T
通讯作者：
Nukiwa T
影响因子：
6
作者：
Goova, MT;Li, J;Schmidt, AM
通讯作者：
Schmidt, AM
高迁移率组盒 1 通过增强 IL-6 依赖性 Th17 同种反应反应促进早期急性同种异体移植排斥
影响因子：
5
作者：
Duan, Lihua;Wang, Cong-Yi;Fang, Min
通讯作者：
Fang, Min
影响因子：
11.1
作者：
Müller, S;Ronfani, L;Bianchi, ME
通讯作者：
Bianchi, ME