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.
Th17 cells require IL-6 and TGFbeta 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(+) TCRbeta(+) 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.
Rachitskaya
Aleksandra V
AV
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hansen
Anna M
AM
Horai
Reiko
R
Li
Zhuqing
Z
Villasmil
Rafael
R
Luger
Dror
D
Nussenblatt
Robert B
RB
Caspi
Rachel R
RR
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; C528688:interleukin-23 receptor, mouse