Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway.
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.
Miellot
Aurore
A
UPRES EA-3408 and Rheumatology Department, University Paris 13 and CHU Avicenne (AP-HP), Bobigny, France.
Zhu
Ren
R
Diem
Séverine
S
Boissier
Marie-Christophe
MC
Herbelin
André
A
Bessis
Natacha
N
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005699:Galactosylceramides / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D016753:Interleukin-10