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, Hiro Take, Hiroshi Nakanishi

Research output: Contribution to journalArticle

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

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Cathepsin H
Toll-Like Receptor 3
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Interferon Regulatory Factor-3
Interferons
Cell Differentiation
Myelin-Oligodendrocyte Glycoprotein
Cysteine Proteases
Dendritic Cells
Multiple Sclerosis
Animal Models
Phosphorylation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

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Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset of EAE though impairment of toll-like receptor 3 cascade. / Okada, Ryo; Zhang, Xinwen; Harada, Yuka; Take, Hiro; Nakanishi, Hiroshi.

In: Inflammation Research, Vol. 67, No. 5, 01.05.2018, p. 371-374.

Research output: Contribution to journalArticle

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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.",
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T1 - Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset of EAE though impairment of toll-like receptor 3 cascade

AU - Okada, Ryo

AU - Zhang, Xinwen

AU - Harada, Yuka

AU - Take, Hiro

AU - Nakanishi, Hiroshi

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AB - 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.

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