Hsp90 controls immune response through spatio-temporal regulation of chaperoned molecule via targeting dendritic cells

最近的研究表明，早期核内体中的toll样受体9 （TLR9）信号传导可导致浆细胞样树突状细胞（pDCs）产生干扰素-a，而晚期核内体中的TLR9信号传导可诱导pDC成熟、IL-6和TNF-a分泌。在这里，我们发现人类DNA以及cpg -寡脱氧核苷酸（ODNs）与热休克蛋白90 （Hsp90）复合物刺激pDCs产生大量IFN-a。Hsp90- cpg -a复合物在dc内化后靶向Rab5^+， EEA1^+-“静态”早期核内体，这表明Hsp90伴随的自身dna / cpg - odn优先分选到静态核内体是通过TLR9信号传导IFN-a产生的必要条件。因此，细胞外Hsp90通过时空调控将惰性的自身dna / cpg - odn转化为IFN-a产生的有效触发器。

Recent studies have suggested that Toll-like recepor 9 (TLR9) signaling in early endosomes leads to interferon-a production by plasmacytoid dendritic cells (pDCs), whereas TLR9 signaling in late endosomes induces pDC maturation, IL-6 and TNF-a secretion. Here we show that human DNA as well as CpG-oligodeoxynucleotides (ODNs) in complex with heat shock protein 90 (Hsp90) stimulate pDCs to produce large quantities of IFN-a. The Hsp90-CpG-A complexes are targeted into the Rab5^+, EEA1^+- "static" early endosome after internalization by DCs, suggesting that preferential sorting of Hsp90 chaperoned self-DNA/CpG-ODNs to the static endosome is required for signaling through TLR9 for IFN-a production. Thus, extracellular Hsp90 converts inert self-DNA/CpG-ODNs into a potent trigger of IFN-a production via spatiotemporal regulation.