ONX-0914, a selective inhibitor of immunoproteasome, ameliorates experimental autoimmune myasthenia gravis by modulating humoral response

J Neuroimmunol. 2017 Oct 15:311:71-78. doi: 10.1016/j.jneuroim.2017.08.005. Epub 2017 Aug 18.

Abstract

Accumulating evidence shows that the immunoproteasome participates in the immune response, beyond its initial role in the protein degradation. Here, we tested the effects of the selective immunoproteasome inhibitor, ONX-0914, on experimental autoimmune myasthenia gravis (EAMG). We found that ONX-0914 ameliorated the severity of ongoing EAMG by reducing the autoantibody affinity, accompanied with decreased Tfh cells and antigen presenting cells. Also it reduced the percentage of Th17 cells and inhibited the secretion of IL-17. Our data indicated ONX-0914 may bring benefit for MG therapy.

Keywords: Experimental autoimmune myasthenia gravis; Humoral immunity; Immunoproteasome; ONX-0914.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / pathology
  • Antigens, CD / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunity, Humoral / drug effects*
  • Immunoglobulin G / blood
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Lymph Nodes / pathology
  • Myasthenia Gravis, Autoimmune, Experimental / drug therapy*
  • Myasthenia Gravis, Autoimmune, Experimental / immunology
  • Oligopeptides / therapeutic use*
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / metabolism*
  • Rats
  • Rats, Inbred Lew
  • Spleen / drug effects
  • Spleen / metabolism
  • T-Lymphocytes, Helper-Inducer / pathology

Substances

  • Antigens, CD
  • Immunoglobulin G
  • Interleukin-17
  • Oligopeptides
  • PR-957
  • Proteasome Inhibitors
  • LMP7 protein
  • Proteasome Endopeptidase Complex