TIRC7 and HLA-DR axis contributes to inflammation in multiple sclerosis.
Mult Scler
; 20(9): 1171-81, 2014 08.
Article
em En
| MEDLINE
| ID: mdl-24526664
ABSTRACT
BACKGROUND AND OBJECTIVE:
Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS).METHODS:
Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model.RESULTS:
TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7(+) T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone.CONCLUSION:
Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Antígenos HLA-DR
/
Células Th1
/
ATPases Vacuolares Próton-Translocadoras
/
Células Th17
/
Esclerose Múltipla
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article