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Invariant natural killer T (iNKT) cells are a subset of innate lymphocytes that recognize lipid antigens in the context of CD1d and mediate potent immune regulatory functions via the rapid production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). We investigated whether diverse Toll-like receptor (TLR) signals in myeloid dendritic cells (DCs) could differentially stimulate iNKT cells. Together with the lipopolysaccharide-detecting receptor TLR4, activation of the nucleic acid sensors TLR7 and TLR9 in DCs were particularly potent in stimulating iNKT cells to produce IFN-gamma, but not IL-4. iNKT cell activation in response to TLR9 stimulation required combined synthesis of type I interferon and de novo production of charged beta-linked glycosphingolipid(s) by DCs. In addition, DCs stimulated via TLR9 activated both iNKT cells and NK cells in vivo and protected mice against B16F10-induced melanoma metastases. These data underline the role of TLR9 in iNKT cell activation and might have relevance to infectious diseases and cancer.

Original publication

DOI

10.1016/j.immuni.2007.08.017

Type

Journal article

Journal

Immunity

Publication Date

10/2007

Volume

27

Pages

597 - 609

Keywords

Acidic Glycosphingolipids, Animals, Antigens, CD1, Antigens, CD1d, Cells, Cultured, Coculture Techniques, Dendritic Cells, Female, Immunotherapy, Adoptive, Interferon Type I, Interferon-gamma, Killer Cells, Natural, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Toll-Like Receptor 7, Toll-Like Receptor 9