Title:New Paradigm for Intrinsic Function of Heat Shock Proteins as Endogenous Ligands in Inflammation and Innate Immunity
Volume: 12
Issue: 9
Author(s): Y. Tamura, T. Torigoe, G. Kutomi, K. Hirata and N. Sato
Affiliation:
Keywords:
Danger signal, dendritic cell, endosome, heat shock protein, innate immunity, Toll-like receptor, ultraviolet radiation, infections, chaperones, tumor, immunogenicity, antigenic peptides, necrosis, T cell, proinflammatory signals
Abstract: 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.