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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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Zhang F, Su X, Huang G, Xin XF, Cao EH, Shi Y, Song Y,


Zhang F, Su X, Huang G, Xin XF, Cao EH, Shi Y, Song Y, (click to view)

Zhang F, Su X, Huang G, Xin XF, Cao EH, Shi Y, Song Y,

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Scientific reports 2017 10 277(1) 14268 doi 10.1038/s41598-017-14667-4
Abstract

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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