研究等業績 - 原著論文 - 海老原 敬
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Ebihara Takashi, Azuma Masahiro, Oshiumi Hiroyuki, Kasamatsu Jun, Iwabuchi Kazuya, Matsumoto Kenji, Saito Hirohisa, Taniguchi Tadatsugu, Matsumoto Misako, Seya Tsukasa
Journal of Experimental Medicine ( Rockefeller University Press ) 207 ( 12 ) 2675 - 2687 2010年 [査読有り]
研究論文（学術雑誌）
In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain-containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1-inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3-dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC-NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC-NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.
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Hepatitis C virus–infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells
Takashi Ebihara, Masashi Shingai, Misako Matsumoto, Takaji Wakita, Tsukasa Seya
Hepatology ( Wiley ) 48 ( 1 ) 48 - 58 2008年07月 [査読有り]
研究論文（学術雑誌）
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Ebihara, T., Masuda, H., Akazawa, T., Shingai, M., Kikuta, H., Ariga, T., Matsumoto, M., Seya, T.
International Immunology 19 ( 10 ) 1145 - 55 2007年 [査読有り]
研究論文（学術雑誌）
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.
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Human Metapneumovirus Infection in Japanese Children
Ebihara, T., Endo, R., Kikuta, H., Ishiguro, N., Ishiko, H., Hara, M., Takahashi, Y., Kobayashi, K.
Journal of Clinical Microbiology ( American Society for Microbiology ) 42 ( 1 ) 126 - 132 2004年 [査読有り]
研究論文（学術雑誌）
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Seroprevalence of human metapneumovirus in Japan
Takashi Ebihara, Rika Endo, Hideaki Kikuta, Nobuhisa Ishiguro, Mikio Yoshioka, Xiaoming Ma, Kunihiko Kobayashi
Journal of Medical Virology ( Wiley ) 70 ( 2 ) 281 - 283 2003年06月 [査読有り]
研究論文（学術雑誌）