Repeated administration of alpha-galactosylceramide ameliorates experimental lupus nephritis in mice.

ABSTRACT: Lupus nephritis is a crucial complication of systemic lupus erythematosus. In this study, we investigated the roles of mouse natural killer T (NKT) cells in lupus nephritis. From 24 weeks of age, NZB/NZW F1 mice were injected with alpha-galactosylceramide (?-GalCer) or vehicle once a week for four weeks. In the ?-GalCer group, the levels of proteinuria and blood urea nitrogen were significantly lower than those in the vehicle group. The histological evaluation showed a decrease in glomerular immune complex deposits and an alleviation of podocyte injury. The proportion of NKT cells in the mononuclear cell (MNC) fraction in the ?-GalCer group was significantly decreased in the liver, kidney, and spleen. The proliferation and cytokine production in ?-GalCer-stimulated liver MNCs were markedly diminished in the ?-GalCer group (anergy). The IFN-? production in liver MNCs stimulated by concanavalin A or an anti-CD3 antibody did not differ between the two groups, whereas the IL-4 production was significantly lower in the ?-GalCer group. In addition, the IgM production in CpG-oligodeoxynucleotide-stimulated spleen MNCs was significantly lower in the ?-GalCer group. These results suggest that ?-GalCer suppressed Th2 immune responses in NKT cells and B cell function, thereby slowing the progression of lupus nephritis.

SUBMITTER: Uchida T 

PROVIDER: S-EPMC5974230 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature