Extracellular Hsp90 Governs Spatio-Temporal Regulation of Biological Responses

  • Yasuaki Tamura
  • Akihiro Yoneda
  • Norio Takei
  • Kaori Sawada
Part of the Heat Shock Proteins book series (HESP, volume 16)


Heat shock protein (HSP) plays a pivotal role in the maintenance of cellular homeostasis within cells. However, recent studies have unveiled unexpected roles of extracellular HSP in various types of biological responses. For example, extracellular Hsp90 facilitates wound healing via recruiting skin cells. In the field of immunology, it has been shown that the historically important and widely studied extracellular HSP-antigenic peptide complex (HSP-PC) activates adaptive immunity through antigen cross-presentation by professional antigen-presenting cells (pAPCs). In addition, extracellular HSP activates innate immunity as a chaperokine and play a role in the etiology of autoimmune diseases including systemic lupus erythematosus. Therefore, the role of extracellular HSP in immunity is now gaining much attention. The most prominent feature of extracellular HSP in immunity is that they function both on their own and as an HSP-ligand complex such as HSP-antigen peptide complex and HSP-nucleic acid complex. Herein, recapitulating the history, we introduce a unique feature of extracellular HSP as a chaperokine: targeting chaperoned molecules into a particular compartment of dendritic cells and thereby inducing innate immune responses via spatiotemporal regulation. Furthermore, we discuss how such chaperokine activity of extracellular HSP impacts the pathogenesis of autoimmune disease and point out that targeting HSP might be an effective therapeutic approach.


Autoimmune disease Chaperokine Dendritic cell Endosome Heat shock protein Toll-like receptor Tumor immunity Wound healing 



Antigen-presenting cell


Cytosine-phosphate- guanine


Dendritic cell


Hypoxia-inducible factor


Heat shock protein


Heat shock protein 72


Heat shock protein 90




Multivesicular body


Systemic lupus erythematosus


Tumor growth factor-β


Toll-like receptor


Tumor necrosis factor



This research was partially supported by the Center of Innovation Program from MEXT and JST.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yasuaki Tamura
    • 1
  • Akihiro Yoneda
    • 1
  • Norio Takei
    • 1
  • Kaori Sawada
    • 1
  1. 1.Department of Molecular Therapeutics, Center for Food & Medical Innovation, Institute for Innovation and Business PromotionHokkaido UniversitySapporoJapan

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