Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Curr Mol Med. 2012 Nov 1;12(9):1198-206. doi: 10.2174/156652412803306710.
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.
最近的研究表明，细胞外热休克蛋白 (HSP) 作为先天和适应性免疫反应的内源性免疫调节剂发挥作用。由于 HSP 在细胞内固有地充当伴侣，因此已经提出了 HSP 释放到细胞外环境的被动释放（如细胞坏死）和主动释放（包括以外泌体形式分泌）。这种细胞外 HSP 已被证明通过 Toll 样受体 (TLR) 激活先天免疫反应。然而，也有人认为 HSP 增强了相关先天配体（如 LPS）刺激细胞因子产生和树突状细胞 (DC) 成熟的能力。更有趣的是，最近的研究表明，内源性和外源性危险信号引发的先天免疫反应在空间和时间上受到调节，并且可以使用 Hsp90 或氧调节蛋白 150 (ORP150) 进行操纵，从而控制免疫反应。我们将讨论抗原呈递细胞内 HSP 伴侣分子的时空调节如何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使我们建立出色的 HSP 为基础的免疫疗法。
