Format

Send to

Choose Destination
Eur J Immunol. 2005 Dec;35(12):3704-13.

Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway.

Author information

1
UPRES EA-3408 and Rheumatology Department, University Paris 13 and CHU Avicenne (AP-HP), Bobigny, France.

Abstract

Invariant natural killer T (iNKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. Agonist alpha-galactosylceramide (alpha-GalCer) of iNKT cells exert a therapeutical effect in type 1 diabetes. We investigated whether iNKT activation with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1 mice, a standard model of rheumatoid arthritis. Here, we have shown that in vivo iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6 mice. alpha-GalCer induced a clear-cut diminution of clinical and histological arthritides. An anti-IL-10 receptor antibody abrogated the protective effect of alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by activated iNKT cells. Confirming these data, disease protection conferred by alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger amounts of IL-10. These findings suggest that in CIA susceptibility to autoimmunity is associated with dysfunctions of iNKT cells. Our demonstration that iNKT cell activation by alpha-GalCer remains efficient in CIA-prone DBA/1 mice to provide protective IL-10 suggests that this could be used therapeutically to treat autoimmune arthritis.

PMID:
16304639
DOI:
10.1002/eji.200535235
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center