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NKT cells constitutively express IL‐23 receptor and RORγt, and rapidly produce IL‐17 upon receptor ligation in an IL‐6‐independent fashion
Author(s) -
Caspi Rachel R,
Rachitskaya Aleksandra V,
Horai Reiko,
Li Zhuqing,
Luger Dror,
Villasmil Rafael,
Nussenblatt Robert B,
Hansen Anna M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1069.5
Subject(s) - natural killer t cell , cd1d , rar related orphan receptor gamma , biology , t cell receptor , microbiology and biotechnology , immunology , receptor , t cell , immune system , foxp3 , biochemistry
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 NKT cells by phenotype (TCRβ + /DX5 + ) and function (response to α–GalCer). Human NKT cells also produced IL‐17 upon stimulation. NKT cells constitutively expressed IL‐23R and RORγt. Ligation of either TCR or IL‐23R triggered IL‐17 production, and both together had an additive effect suggesting independent pathways. IL‐17 was produced exclusively by the NK1.1 − fraction, but was not restricted to a particular subset of NKT cells, as the NKT populations of Jα18 −/− and of CD1d −/− mice, which lack certain NKT subsets, produced IL‐17. Importantly, in vivo administration of α–GalCer 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.