Cathepsin C modulates myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis

Wilaiwan Wisessmith Durose, Takahiro Shimizu, Jia Yi Li, Manabu Abe, Kenji Sakimura, Banthit Chetsawang, Kenji Tanaka, Akio Suzumura, Koujiro Tohyama, Kazuhiro Ikenaka

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Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by immune-mediated inflammation, which attacks the myelin sheath. MS pursues a relapsing and remitting course with varying intervals between symptoms. The main clinical pathological features include inflammation, myelin sheath destruction and plaque formation in the central nervous system (CNS). We previously reported that cystatin F (CysF) expression is induced in demyelinating lesions that are accompanied by active remyelination (referred to as shadow plaques) but is down-regulated in chronic demyelinated lesions (plaques) in the spinal cord of MS patients and in several murine models of demyelinating disease. CysF is a cathepsin protease inhibitor whose major target is cathepsin C (CatC), which is co-expressed in demyelinating regions in Plp4e/− mice, a model of chronic demyelination. Here, we report the time course of CatC and CysF expression and describe the symptoms in a mouse experimental autoimmune encephalomyelitis (EAE) model using CatC knockdown (KD) and CatC over-expression (OE) mice. In myelin oligodendrocyte glycoprotein (MOG)-EAE, CatC positive cells were found to infiltrate the CNS at an early stage prior to any clinical signs, in comparison to WT mice. CysF expression was not observed at this early stage, but appeared later within shadow plaques. CatC expression was found in chronic demyelinated lesions but was not associated with CysF expression, and CatCKD EAE mouse showed delayed demyelination. Whereas, CatCOE in microglia significantly increased severity of demyelination in the MOG-EAE model. Thus, these results demonstrate that CatC plays a major role in MOG-EAE. (Figure presented.).

Original languageEnglish
JournalJournal of Neurochemistry
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Keywords

  • cathepsin C
  • cystatin F
  • demyelination
  • experimental autoimmune encephalomyelitis (EAE)
  • multiple sclerosis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Durose, W. W., Shimizu, T., Li, J. Y., Abe, M., Sakimura, K., Chetsawang, B., Tanaka, K., Suzumura, A., Tohyama, K., & Ikenaka, K. (Accepted/In press). Cathepsin C modulates myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Journal of Neurochemistry. https://doi.org/10.1111/jnc.14581