NKT cells are endowed with potent regulatory functions during the immune response, rendering their investigation in immunopathological situations particularly relevant. During my PhD studies I have examined the impact of iNKT cell deficiencies in NOD mice, using two autoimmune settings, namely type 1 diabetes and ConA-induced hepatitis. NOD mice develop insulin-dependent diabetes spontaneously. Their iNKT cell population is reduced, and even though it does not ensure protection against diabetes as such, it constitutes a sensitive therapeutic target of a-GalCer, which prevents the onset of the disease. On the other hand, we found that NOD mice were less prone to ConA-induced hepatitis than wild-type mice and provide evidence for a deleterious role of spleen- rather than liver-derived IL-4 in this pathology. Finally, we demonstrate that IL-12, acknowledged for its capacity to exacerbate the disease, can directly enhance IL-4 production by spleen iNKT cells. Taken together, our study reveals new therapeutic targets for immuno-intervention and highlights once again the contrasting biological effects of iNKT cells, both beneficial and detrimental.
