Extracellular lysosome-associated membrane protein-1 (LAMP-1) mediates autoimmune disease progression in the NOD model of type 1 diabetes.
Fiche publication
Date publication
mai 2005
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DE CARVALHO BITTENCOURT Marcelo
Tous les auteurs :
De Carvalho Bittencourt M, Herren S, Graber P, Vilbois F, Pasquali C, Berney C, Plitz T, Nicoletti F, Kosco-Vilbois MH
Lien Pubmed
Résumé
Treatment (from 5 to 25 weeks of age) with a novel blocking monoclonal antibody, mAb I-10, directed against the plasma membrane (pm) form of LAMP-1, protected against development of autoimmune diabetes in the NOD mouse. A shorter course of treatment, i.e. from 5 to 12 weeks of age, significantly reduced the occurrence of insulitis as well as disease onset. Interfering with pm-LAMP-1 required continuous treatment as tolerance was not observed when treatment was stopped, and no higher proportion of cells with a T regulatory phenotype (e.g. CD4(+)CD25(+)) were induced. The mechanism appears to involve modulating a proinflammatory cytokine, as the proportion of pancreatic-infiltrating IFN-gamma-positive cells was significantly reduced in the mAb I-10-treated group. These results demonstrate an unexpected role for pm-LAMP-1 in autoimmune disease progression, and suggest that further investigation should be performed to understand how this molecule modulates IFN-gamma-driven responses.
Référence
Eur J Immunol. 2005 May;35(5):1501-9.