title: Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection.
abstract: Monocyte-derived dendritic cells (mDCs) and NK cells are reciprocally activate via cytokines and cell-cell contact. Although seven human NKG2D ligands (NKG2DLs), UL16-binding proteins (ULBP) 1, 2, 3 and 4, retinoic acid early transcript 1G (RAET1G) and MHC class I-related chains A and B, have been reported, the differential distribution and roles of these ligands in the maturation of human mDCs have not been elucidated. In the present study, we produced polyclonal antibodies (pAbs) directed against human ULBP1, 2 and 3. All these ULBPs were detected on human mDCs when probed by the pAbs, although their expression profiles were different. We next investigated what kinds of Toll-like receptor agonists and RNA viruses [influenza virus, human respiratory syncytial virus (RSV), measles virus and hepatitis C virus (HCV)] induced the expression of NKG2DLs on mDCs. ULBP1 was up-regulated on mDCs in response to LPS or infection with RSV. The expression of ULBP2 was induced by LPS and poly I:C, indicating that the TIR-containing adapter molecule-1 (TIR domain-containing adaptor-inducing IFN) pathway is associated with ULBP2 induction. Although infection with HCV did not cause up-regulation of NKG2DLs, other RNA virus infections and poly I:C promoted expression of ULBP2 and RAET1G in an IFN-alpha/beta-independent manner. Finally, the over-expression of ULBP1 and 2 on mDCs facilitated NK cell proliferation and IFN-gamma production through a mDC-NK cell interaction in the presence of IL-2. Hence, the results reflect the important role of NKG2DLs on human mDCs in mDC-mediated NK cell activation.
authors: Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
authors: Takashi
authors: T
authors: Ebihara
authors: Hisayo
authors: H
authors: Masuda
authors: Takashi
authors: T
authors: Akazawa
authors: Masashi
authors: M
authors: Shingai
authors: Hideaki
authors: H
authors: Kikuta
authors: Tadashi
authors: T
authors: Ariga
authors: Misako
authors: M
authors: Matsumoto
authors: Tsukasa
authors: T
authors: Seya
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011070:Poly I-C / Q000494:pharmacology; D012328:RNA Viruses / Q000276:immunology*; D011971:Receptors, Immunologic / Q000819:agonists*; D055607:Receptors, Natural Killer Cell; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000906:Antibodies; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D051193:Toll-Like Receptors; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human; D007371:Interferon-gamma; D011070:Poly I-C