Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset of EAE though impairment of toll-like receptor 3 cascade.
Inflamm Res
; 67(5): 371-374, 2018 May.
Article
em En
| MEDLINE
| ID: mdl-29470604
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(IC)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-ß (IFN-ß) by splenocytes. RESULTS ANDCONCLUSIONS:
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(IC)-induced increased TLR3 expression, interferon regulatory factor 3 (IRF3) phospholylation and IFN-ß secretion. Therefore, CatH deficiency impaired TLR3-mediated activation of IRF3 and consequent secretion of IFN-ß from dendritic cells, leading to the enhancement of Th1 cell differentiation and consequent early disease onset of EAE.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Th1
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Encefalomielite Autoimune Experimental
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Receptor 3 Toll-Like
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Catepsina H
/
Ativação de Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article