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

Nature Medicine volume 9, pages 14691476 (2003) | Download Citation

Abstract

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.

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Acknowledgements

This study was supported by a Canadian Institute for Health Research operating grant and CANVAC Network Centres of Excellence. D.G.M. is the recipient of a Canadian Diabetes Association Fellowship. K.M.G. is supported by National Institutes of Health grants S06GM08012 and SG12RR08124. Z.L. is supported in part by NIH grant CA90337. P.S.O. holds a Canada Research Chair in Infection and Immunity.

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Affiliations

  1. Departments of Immunology and Medical Biophysics, University Health Network, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada.

    • Douglas G Millar
    • , Alisha R Elford
    • , Nobuyuki Ono
    •  & Pamela S Ohashi
  2. Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas 79968, USA.

    • Kristine M Garza
  3. Institute of Pathology, Department of Experimental Pathology, University Hospital, 8091 Zurich, Switzerland.

    • Bernhard Odermatt
  4. Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut, Farmington, Connecticut 06030, USA.

    • Zihai Li

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Pamela S Ohashi.

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https://doi.org/10.1038/nm962

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