Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo

被引:218
作者
Millar, DG
Garza, KM
Odermatt, B
Elford, AR
Ono, N
Li, Z
Ohashi, PS [1 ]
机构
[1] Ontario Canc Inst, Univ Hlth Network, Dept Immunol, Toronto, ON M5G 2M9, Canada
[2] Ontario Canc Inst, Univ Hlth Network, Dept Med Biophys, Toronto, ON M5G 2M9, Canada
[3] Univ Texas, Dept Biol Sci, El Paso, TX 79968 USA
[4] Univ Zurich Hosp, Dept Expt Pathol, Inst Pathol, CH-8091 Zurich, Switzerland
[5] Univ Connecticut, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT 06030 USA
关键词
D O I
10.1038/nm962
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pathogens or pathogen- associated molecular patterns can signal to cells of the innate immune system and trigger effective adaptive immunity. However, relatively little is known about how the innate immune system detects tissue injury or necrosis. Evidence suggests that the release of heat- shock proteins (HSPs) may provide adjuvant- like signals, but the ability of HSPs to promote activation or tolerance in vivo has not been addressed. In this study we show that Hsp70 promotes dendritic cell (DC) function and, together with antigen, triggers autoimmune disease in vivo.
引用
收藏
页码:1469 / 1476
页数:8
相关论文
共 60 条
[1]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[2]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[3]  
Asea A, 2000, CELL STRESS CHAPERON, V5, P425, DOI 10.1379/1466-1268(2000)005<0425:HPBAPN>2.0.CO
[4]  
2
[5]   Novel signal transduction pathway utilized by extracellular HSP70 -: Role of Toll-like receptor (TLR) 2 AND TLR4 [J].
Asea, A ;
Rehli, M ;
Kabingu, E ;
Boch, JA ;
Baré, O ;
Auron, PE ;
Stevenson, MA ;
Calderwood, SK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (17) :15028-15034
[6]   HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine [J].
Asea, A ;
Kraeft, SK ;
Kurt-Jones, EA ;
Stevenson, MA ;
Chen, LB ;
Finberg, RW ;
Koo, GC ;
Calderwood, SK .
NATURE MEDICINE, 2000, 6 (04) :435-442
[7]   Immunobiology of dendritic cells [J].
Banchereau, J ;
Briere, F ;
Caux, C ;
Davoust, J ;
Lebecque, S ;
Liu, YT ;
Pulendran, B ;
Palucka, K .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+
[8]   Signaling through OX40 (CD134) breaks peripheral T-cell tolerance [J].
Bansal-Pakala, P ;
Jember, AGH ;
Croft, M .
NATURE MEDICINE, 2001, 7 (08) :907-912
[9]   Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway [J].
Basu, S ;
Binder, RJ ;
Suto, R ;
Anderson, KM ;
Srivastava, PK .
INTERNATIONAL IMMUNOLOGY, 2000, 12 (11) :1539-1546
[10]   CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin [J].
Basu, S ;
Binder, RJ ;
Ramalingam, T ;
Srivastava, PK .
IMMUNITY, 2001, 14 (03) :303-313