Thymic-Specific Serine Protease Limits Central Tolerance and Exacerbates Experimental Autoimmune Encephalomyelitis.
J Immunol
; 199(11): 3748-3756, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29061767
ABSTRACT
The genetic predisposition to multiple sclerosis (MS) is most strongly conveyed by MHC class II haplotypes, possibly by shaping the autoimmune CD4 T cell repertoire. Whether Ag-processing enzymes contribute to MS susceptibility by editing the peptide repertoire presented by these MHC haplotypes is unclear. Thymus-specific serine protease (TSSP) is expressed by thymic epithelial cells and thymic dendritic cells (DCs) and, in these two stromal compartments, TSSP edits the peptide repertoire presented by class II molecules. We show in this article that TSSP increases experimental autoimmune encephalomyelitis severity by limiting central tolerance to myelin oligodendrocyte glycoprotein. The effect on experimental autoimmune encephalomyelitis severity was MHC class II allele dependent, because the lack of TSSP expression conferred protection in NOD mice but not in C57BL/6 mice. Importantly, although human thymic DCs express TSSP, individuals segregate into two groups having a high or 10-fold lower level of expression. Therefore, the level of TSSP expression by thymic DCs may modify the risk factors for MS conferred by some MHC class II haplotypes.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Células Dendríticas
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Serina Endopeptidases
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Encefalomielite Autoimune Experimental
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Células Epiteliais
/
Esclerose Múltipla
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França