Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset of EAE though impairment of toll-like receptor 3 cascade

Ryo Okada, Xinwen Zhang, Yuka Harada, Zhou Wu, Hiroshi Nakanishi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Objective: The objective of this study is to investigate the role of cathepsin H (CatH), a lysosomal cysteine protease, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Methods: EAE was induced in CatH-deficient mice (CatH−/−) and wild-type littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35–55. The effects of CatH deficiency were determined by clinical scoring, mRNA expression levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-β (IFN-β) by splenocytes. Results and conclusions: CatH−/− showed a significantly earlier disease onset of EAE and increased Th1 cell differentiation in splenocytes. Splenocytes prepared from immunized CatH−/− showed a significant decrease in poly(I:C)-induced increased TLR3 expression, interferon regulatory factor 3 (IRF3) phospholylation and IFN-β secretion. Therefore, CatH deficiency impaired TLR3-mediated activation of IRF3 and consequent secretion of IFN-β from dendritic cells, leading to the enhancement of Th1 cell differentiation and consequent early disease onset of EAE.

Original languageEnglish
Pages (from-to)371-374
Number of pages4
JournalInflammation Research
Volume67
Issue number5
DOIs
Publication statusPublished - May 1 2018

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

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