Immunomodulatory properties of cystatins

Cell Mol Life Sci. 2002 Sep;59(9):1503-12. doi: 10.1007/s00018-002-8525-4.


Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in all living organisms and because they are involved in various biological and pathological processes, the control of these protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation. They also induce tumor necrosis factor alpha and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon gamma-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of this property, leading to practical applications in immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cathepsins / metabolism
  • Cystatins / genetics
  • Cystatins / immunology*
  • Cystatins / metabolism
  • Cysteine Proteinase Inhibitors / genetics
  • Cysteine Proteinase Inhibitors / immunology*
  • Cysteine Proteinase Inhibitors / metabolism
  • Cytokines / metabolism
  • Helminth Proteins / genetics
  • Helminth Proteins / immunology
  • Helminth Proteins / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nitric Oxide / metabolism
  • Protein Structure, Tertiary
  • Sequence Alignment
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Wolbachia / metabolism


  • Cystatins
  • Cysteine Proteinase Inhibitors
  • Cytokines
  • Helminth Proteins
  • Nitric Oxide
  • Cathepsins