Cutting edge:: NKT cells constitutively express IL-23 receptor and RORγt and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion

Th17 cells require IL-6 and TGF beta for lineage commitment and IL-23 for maintenance. Unexpectedly, naive IL-6(-/-) splenocytes stimulated with anti-CD3 and IL-23 produced normal amounts of IL-17 during the first 24 h of culture. These rapid IL-6-independent IL-17 producers were identified as predominantly DX5+ TCR beta(+) NKT cells, and a comparable response could be found using the invariant NKT-specific ligand a galactosylceramide. Human NKT cells also produced IL-17. NKT cells constitutively expressed IL-23R and ROR gamma t. Ligation of either TCR or IL-23R triggered IL-17 production and both together had a synergistic effect, suggesting independent but convergent pathways. IL-17 production was not restricted to a particular subset of NKT cells but they were NK1.1 negative. Importantly, in vivo administration of a galactosylceramide triggered a rapid IL-17 response in the spleen. These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response.