Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo.
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.
Millar
Douglas G
DG
Departments of Immunology and Medical Biophysics, University Health Network, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada.
Garza
Kristine M
KM
Odermatt
Bernhard
B
Elford
Alisha R
AR
Ono
Nobuyuki
N
Li
Zihai
Z
Ohashi
Pamela S
PS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015551:Autoimmunity; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D019013:CD40 Antigens; D018076:DNA, Complementary; D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D018664:Interleukin-12