New paradigm for intrinsic function of heat shock proteins as endogenous ligands in inflammation and innate immunity.
New paradigm for intrinsic function of heat shock proteins as endogenous ligands in inflammation and innate immunity.
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DOI：
10.2174/156652412803306710
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发表时间：
2012-10
影响因子：
2.5
通讯作者：
Y. Tamura;T. Torigoe;G. Kutomi;K. Hirata;N. Sato
中科院分区：
文献类型：
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作者：
Y. Tamura;T. Torigoe;G. Kutomi;K. Hirata;N. Sato
近年来，越来越多的证据表明，细胞外热休克蛋白（HSP）作为内源性免疫调节剂参与了先天性和适应性免疫应答。由于HSP固有地充当细胞内的分子伴侣，因此已经提出HSP释放到细胞外环境中的被动释放（例如细胞坏死）和主动释放（包括外泌体形式的分泌）。已显示此类细胞外HSP是通过Toll样受体（TLR）的先天免疫应答的激活剂。然而，也有人提出，热休克蛋白增强相关的先天性配体，如LPS刺激细胞因子的产生和树突状细胞（DC）的成熟的能力。更有趣的是，最近的研究表明，由内源性和外源性危险信号引起的先天免疫反应在空间和时间上受到调节，并且这可以使用Hsp90或氧调节蛋白150（ORP 150）来操纵，从而控制免疫反应。我们将讨论如何时空调节抗原呈递细胞内的HSP分子伴侣影响抗原交叉呈递和先天免疫反应。对HSP生物学的精确分析可以引导我们建立出色的基于HSP的免疫疗法。
Recently, growing evidences that extracellular heat shock protein (HSP) functions as endogenous immunomodulator for innate and adaptive immune responses have been demonstrated. Because HSPs inherently act as chaperones within the cells, passive release such as cell necrosis and active release including secretion in the form of exosome have been suggested for HSP release into extracellular milieu. Such extracellular HSPs have been shown to be activators for innate immune responses through Toll-like receptors (TLRs). However, it has also been suggested that HSPs augmented the ability of associated innate ligands such as LPS to stimulate cytokine production and dendritic cell (DC) maturation. More interestingly, recent study demonstrated that innate immune responses elicited by both endogenous and exogenous danger signals were spatially and temporally regulated and this can be manipulated using Hsp90 or oxygen-regulated protein 150 (ORP150), thereby controlling the immune responses. We will discuss how spatiotemporal regulation of HSP-chaperoned molecules within antigen-presenting cells affects the antigen cross-presentation and innate immune responses. Precise analysis of HSP biology can lead us to establish outstanding HSPbased immunotherapy.