On the role of the immunoproteasome in transplant rejection

Immunogenetics. 2019 Mar;71(3):263-271. doi: 10.1007/s00251-018-1084-0. Epub 2018 Sep 15.

Abstract

The immunoproteasome is expressed in cells of hematopoietic origin and is induced during inflammation by IFN-γ. Targeting the immunoproteasome with selective inhibitors has been shown to be therapeutically effective in pre-clinical models for autoimmune diseases, colitis-associated cancer formation, and transplantation. Immunoproteasome inhibition prevents activation and proliferation of lymphocytes, lowers MHC class I cell surface expression, reduces the expression of cytokines of activated immune cells, and curtails T helper 1 and 17 cell differentiation. This might explain the in vivo efficacy of immunoproteasome inhibition in different pre-clinical disease models for autoimmunity, cancer, and transplantation. In this review, we summarize the effect of immunoproteasome inhibition in different animal models for transplantation.

Keywords: Antigen presentation; Antigen processing; Immunoproteasome; Proteasome; Transplantation.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / therapy*
  • Graft Rejection / drug therapy
  • Graft Rejection / enzymology
  • Graft Rejection / etiology*
  • Histocompatibility Antigens Class I / drug effects
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Organ Transplantation / adverse effects*
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / therapeutic use*
  • Signal Transduction

Substances

  • Histocompatibility Antigens Class I
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex