Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice.
Diabetes
; 73(5): 806-818, 2024 May 01.
Article
em En
| MEDLINE
| ID: mdl-38387059
ABSTRACT
Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed in pancreatic islets, leading to the destruction of insulin-producing ß-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the ß-cell surface. This unique molecular target offers the potential to shield ß-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 could home in on pancreatic islets and prevent autoantibodies from recognizing ß-cells. This study demonstrates that mAb43 binds to exocytotic sites on the ß-cell surface, masking the antigenic exposure of ZnT8 and insulin after glucose-stimulated insulin secretion. In vivo administration of mAb43 to NOD mice selectively increased the proportion of regulatory T cells in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation, and no adverse effects were exhibited during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of ß-cells suppresses the immunological cascade from B-cell antigen presentation to T cell-mediated ß-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Diabetes Mellitus Tipo 1
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2024
Tipo de documento:
Article