Extracellular Hsp90 plays a pivotal role in innate immunity and adaptive immunity

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659165
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: SATO Noriyuki 札幌医科大学, 医学部, 教授 (50158937)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 熱ショック蛋白質 / 無菌性炎症 / 自然免疫 / 獲得免疫 / 樹状細胞 / クロスプレゼンテーション / 酸化酵素

Outline of Final Research Achievements

Extracellular heat shock proteins (HSPs) have been shown to initiate an aseptic inflammation via an activation of antigen presenting cells including dendritic cells. Moreover, we have shown that extracellular Hsp90-antigen complex is efficiently cross-presented by dendritic cells and stimulates antigen-specific T cells. Thus, extracellular Hsp90 plays a crucial role in the activation of innate immunity and adaptive immunity. In this study, we have identified ER-resident oxidase ERO1-α as a candidate of Hsp90 receptor. The cell surface expression as well as ER expression of ERO1-α was augmented when dendritic cells were exposed to hypoxia and oxidative stress caused by H2O2 treatment. Extracellular Hsp90 bound to ERO1-α expressed on the cell surface of dendritic cells. We are currently investigating whether ERO1-α-bound Hsp90 is endocytosed and activates dendritic cells. These results will explain how endogenous extracellular HSPs impact on the inflammation and immunity.

Free Research Field

病理学