The dual immunoregulatory roles of stress proteins

Trends Biochem Sci. 2008 Feb;33(2):71-9. doi: 10.1016/j.tibs.2007.10.005. Epub 2008 Jan 7.


Stress proteins (SPs) from the heat shock and glucose-regulated protein families are abundant intracellular molecules that have powerful extracellular roles as immune modulators. Mammalian immune cells encounter both identical (self) SPs and non-identical SPs derived from invading pathogens. Although such extracellular SPs can function as powerful immunological adjuvants, SPs, including Hsp60 and Hsp70, can also attenuate inflammatory disease via apparent effects on immunoregulatory T cell populations. It therefore seems that the immunostimulatory and immunosuppressive potential of extracellular SPs depends on the context in which they are encountered by the cellular immune-response network. Conclusions regarding the immunobiology of these powerful immunomodulatory molecules must therefore take into account their dichotomous properties and their physiological role and importance must be interpreted in the context of the complex in vivo microenvironments in which these proteins exist.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / immunology*
  • Immune System / physiology*
  • Immunosuppressive Agents / immunology
  • Lymphocyte Subsets / immunology
  • Molecular Chaperones / immunology
  • Receptors, Cell Surface / immunology
  • T-Lymphocytes / immunology


  • Antigens, Neoplasm
  • Heat-Shock Proteins
  • Immunosuppressive Agents
  • Molecular Chaperones
  • Receptors, Cell Surface