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

AV Rachitskaya, AM Hansen, R Horai, Z Li… - The Journal of …, 2008 - journals.aai.org
AV Rachitskaya, AM Hansen, R Horai, Z Li, R Villasmil, D Luger, RB Nussenblatt, RR Caspi
The Journal of Immunology, 2008journals.aai.org
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 …
Abstract
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.
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