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Cutting Edge: NKT Cells Constitutively Express IL-23 Receptor and RORgammat and Rapidly Produce IL-17 upon Receptor Ligation in an IL-6-Independent Fashion Export

J Immunol, Vol. 180, No. 8. (15 April 2008), pp. 5167-5171.

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il-17 il-23 il-6 interleukin nkt ror

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


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