Th17 cells require IL-6 and TGFβ 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+ TCRβ+ NKT cells, and a comparable response could be found using the invariant NKT-specific ligand α-galactosylceramide. Human NKT cells also produced IL-17. NKT cells constitutively expressed IL-23R and RORγt. 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 α-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.

The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.