Open AccessInhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis
Author(s) -
Basler Michael,
Mundt Sarah,
Muchamuel Tony,
Moll Carlo,
Jiang Jing,
Groettrup Marcus,
Kirk Christopher J.
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303543
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , immunology , encephalomyelitis , demyelinating disease , immune system , cytokine , proteasome , autoimmune disease , chemistry , biology , microbiology and biotechnology , antibody
Multiple sclerosis ( MS ) is a chronic demyelinating immune mediated disease of the central nervous system. The immunoproteasome is a distinct class of proteasomes found predominantly in monocytes and lymphocytes. Recently, we demonstrated a novel function of immunoproteasomes in cytokine production and T cell differentiation. In this study, we investigated the therapeutic efficacy of an inhibitor of the immunoproteasome ( ONX 0914) in two different mouse models of MS . ONX 0914 attenuated disease progression after active and passive induction of experimental autoimmune encephalomyelitis ( EAE ), both in MOG 35–55 and PLP 139–151 ‐induced EAE . Isolation of lymphocytes from the brain or spinal cord revealed a strong reduction of cytokine‐producing CD 4 + cells in ONX 0914 treated mice. Additionally, ONX 0914 treatment prevented disease exacerbation in a relapsing‐remitting model. An analysis of draining lymph nodes after induction of EAE revealed that the differentiation to Th17 or Th1 cells was strongly impaired in ONX 0914 treated mice. These results implicate the immunoproteasome in the development of EAE and suggest that immunoproteasome inhibitors are promising drugs for the treatment of MS .