研究等業績 - その他 - 海老原　敬

第1土曜特集 自然リンパ球の生理と病理 ILC2と疲弊

海老原 敬, 山田 俊樹

医学のあゆみ ( 医歯薬出版 )  288 ( 1 ) 43 - 47   2024年01月

DOI CiNii Research

2型自然リンパ球の訓練免疫

海老原 敬

【COPDと気管支喘息、その周辺疾患-病態・診断・治療の最新動向-】喘息病態up-to-date   80   586 - 590   2022年

CiNii Research

抗原受容体をもたないリンパ球 NK細胞

海老原 敬

臨床検査   66   583 - 587   2022年

CiNii Research

Ccr4-NOT脱アデニル化酵素複合体は抗腫瘍性NK細胞活性を制御する(The Ccr4-Not deadenylase complex controls antitumor NK cell activity)

Tatematsu Megumi, Sawa Shinichiro, Ikuta Koichi, Ebihara Takashi

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  50 ( Proceedings ) 3 - P   2021年11月

研究発表要旨（全国大会，その他学術会議）  

ILC2の活性化により生じる細胞死は慢性アレルギー性炎症に対し保護的に働く(Activation-induced cell death of ILC2s confersprotection against chronic allergic inflammation)

Yamada Toshiki, Tatematsu Megumi, Ebihara Takashi

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  50 ( Proceedings ) 3 - P   2021年11月

研究発表要旨（全国大会，その他学術会議）  

肝特異的ホスファチジルグリセロールリン酸ホスファターゼ遺伝子欠損によるラロン型低身長症様疾患モデルマウス

高須賀 俊輔, 海老原 敬, 佐々木 雄彦

日本生化学会大会プログラム・講演要旨集 ( (公社)日本生化学会 )  94回   [P - 991]   2021年11月

研究発表要旨（全国大会，その他学術会議）  

新規慢性閉塞性肺疾患モデルにおける免疫細胞の機能解析

海老原 敬

医科学応用研究財団研究報告 ( (公財)鈴木謙三記念医科学応用研究財団 )  37   227 - 230   2020年02月

その他記事  

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis

Amanda Ardain, Racquel Domingo-Gonzalez, Shibali Das, Samuel W. Kazer, Nicole C. Howard, Alveera Singh, Mushtaq Ahmed, Shepherd Nhamoyebonde, Javier Rangel-Moreno, Paul Ogongo, Lan Lu, Duran Ramsuran, Maria de la Luz Garcia-Hernandez, Tyler K. Ulland, Matthew Darby, Eugene Park, Farina Karim, Laura Melocchi, Rajhmun Madansein, Kaylesh Jay Dullabh, Micah Dunlap, Nancy Marin-Agudelo, Takashi Ebihara, Thumbi Ndung’u, Deepak Kaushal, Alexander S. Pym, Jay K. Kolls, Adrie Steyn, Joaquín Zúñiga, William Horsnell, Wayne M. Yokoyama, Alex K. Shalek, Henrik N. Kløverpris, Marco Colonna, Alasdair Leslie, Shabaana A. Khader

Nature ( Springer Science and Business Media LLC )  570 ( 7762 ) 528 - 532   2019年06月

DOI

T細胞(1) T細胞発生とレパートリー選択 免疫系の発達におけるC末端アミノ酸配列によるRunx3活性の制御(T cell: T cell development and repertoire selection Regulation of Runx3 activity in immune system development by the C-terminal end amino acid sequence)

Kojo Satoshi, Ebihara Takashi, Ohno-Oishi Michiko, Muroi Sawako, Taniuchi Ichiro

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  46 ( Proceedings ) 2 - O/P   2017年12月

研究発表要旨（全国大会，その他学術会議）  

免疫システム開発 免疫細胞発生におけるRunx転写因子の役割(Immunosystem development Roles of Runx Transcription Factors In Immune Cell Development)

Taniuchi Ichiro, Kojo Satoshi, Ebihara Takashi, Seo Wooseok, Tenno Mari

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  46 ( Proceedings ) S8 - 5   2017年12月

研究発表要旨（全国大会，その他学術会議）  

自然リンパ球(2) (ILC1,2,3) Runxタンパク質はILC2の構成的活性を抑制し活性化後のILC2枯渇を予防する(Innate Lymphocyte (ILC1,2,3) Runx proteins suppress constitutive activity of ILC2 and prevent ILC2 exhaustion after activation)

Ebihara Takashi, Kojo Satoshi, Taniuchi Ishiro

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  46 ( Proceedings ) 3 - O/P   2017年12月

研究発表要旨（全国大会，その他学術会議）  

免疫学の進歩と神経免疫学への応用 Innate Lymphoid cells 分化プログラムと機能

海老原 敬

神経免疫学 ( (一社)日本神経免疫学会 )  22 ( 1 ) 65 - 65   2017年10月

講演資料等（セミナー，チュートリアル，講習，講義他）  

Immunoreceptor tyrosine-based inhibitory motif–dependent functions of an MHC class I-specific NK cell receptor

Bern, M.D., Beckman, D.L., Ebihara, T., Taffner, S.M., Poursine-Laurent, J., White, J.M., Yokoyama, W.M.

Proceedings of the National Academy of Sciences of the United States of America   114 ( 40 )   2017年

DOI

Roles of RUNX complexes in immune cell development

Ebihara, T., Seo, W., Taniuchi, I.

Advances in Experimental Medicine and Biology ( Advances in Experimental Medicine and Biology )  962   2017年

DOI

Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy

Azuma, M., Takeda, Y., Nakajima, H., Sugiyama, H., Ebihara, T., Oshiumi, H., Matsumoto, M., Seya, T.

OncoImmunology   5 ( 8 )   2016年

DOI

自然リンパ球 成人の腸におけるILC1およびILC3に特異的な前駆細胞の同定(Innate lymphocytes Identification of progenitor cells specific to ILC1s and ILC3s in adult intestine)

Ebihara Takashi, Egawa Takeshi, Yokoyama M. Wayne

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  44 ( Proceedings ) 40 - 40   2015年10月

研究発表要旨（全国大会，その他学術会議）  

Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation (vol 207, pg 2675, 2010)

Takashi Ebihara, Masahiro Azuma, Hiroyuki Oshiumi, Jun Kasamatsu, Kazuya Iwabuchi, Kenji Matsumoto, Hirohisa Saito, Tadatsugu Taniguchi, Misako Matsumoto, Tsukasa Seya

JOURNAL OF EXPERIMENTAL MEDICINE ( ROCKEFELLER UNIV PRESS )  212 ( 8 ) 1337 - 1337   2015年07月

DOI PubMed

【自然リンパ球】ILC1とNK細胞

海老原 敬

医学のあゆみ ( 医歯薬出版(株) )  251 ( 6 ) 494 - 498   2014年11月

Innate lymphocyte 1(ILC1)はIFN-γを産生する自然リンパ球の総称であるが、他のILCと比べて、まだよく解析が進んでいない。最大の理由はnatural killer(NK)細胞、とくに組織に存在するNK細胞(tissue-resident NK細胞:trNK細胞)との類似性のためである。しかし、すべてのILCに分化する前駆細胞の発見により、NK細胞はILC1とは異なる細胞であることが明らかになってきた。とくに肝のtrNK細胞・ILC1は免疫記憶の可能性をもつため、注目を浴びている。一方、NK細胞領域ではサイトカイン刺激やウイルス感染後に長期に生存するNK細胞、ライセンシング(エデュケーション)が盛んに研究されている。本稿では、これらの最新の知見を総説する。(著者抄録)

自然リンパ系細胞-1 自然リンパ系細胞におけるRunx3の差別的役割(Innate lymphoid cells Differential roles of Runx3 in innate lymphoid cells)

Ebihara Takashi, Egawa Takeshi, Song Christina, Colonna Marco, Yokoyama Wayne M.

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  43 ( Proceedings ) 33 - 33   2014年11月

INAM Plays a Critical Role in IFN-γ Production by NK Cells Interacting with Polyinosinic-Polycytidylic Acid–Stimulated Accessory Cells

Jun Kasamatsu, Masahiro Azuma, Hiroyuki Oshiumi, Yuka Morioka, Masaru Okabe, Takashi Ebihara, Misako Matsumoto, Tsukasa Seya

The Journal of Immunology ( The American Association of Immunologists )  193 ( 10 ) 5199 - 5207   2014年10月

© 2014 by The American Association of Immunologists, Inc. Polyinosinic-polycytidylic acid strongly promotes the antitumor activity ofNKcells via TLR3/Toll/IL-1R domain-containing adaptor molecule 1 and melanoma differentiation-associated protein-5/mitochondrial antiviral signaling protein pathways. Polyinosinicpolycytidylic acid acts on accessory cells such as dendritic cells (DCs) and macrophages (Mφs) to secondarily activate NK cells. In a previous study in this context, we identified a novel NK-activating molecule, named IFN regulatory factor 3-dependent NKactivating molecule (INAM), a tetraspanin-like membrane glycoprotein (also called Fam26F). In the current study, we generated INAM-deficient mice and investigated the in vivo function of INAM.We found that cytotoxicity against NK cell-sensitive tumor cell lines was barely decreased in Inam-/- mice, whereas the number of IFN-γ-producing cells was markedly decreased in the early phase. Notably, deficiency of INAM in NK and accessory cells, such as CD8α+ conventional DCs and Mφs, led to a robust decrease in IFN-γ production. In conformity with this phenotype, INAM effectively suppressed lung metastasis of B16F10 melanoma cells, which is controlled by NK1.1+ cells and IFN-γ. These results suggest that INAM plays a critical role in NK-CD8α+ conventional DC (and Mφ) interaction leading to IFN-γ production from NK cells in vivo. INAM could therefore be a novel target molecule for cancer immunotherapy against IFN-γ-suppressible metastasis.

DOI PubMed

MAVS-dependent IRF3/7 bypass of interferon p-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells

Takaki Hiromi, Honda Kenya, Atarashi Koji, Kobayashi Fukiko, Ebihara Takashi, Oshiumi Hiroyuki, Matsumoto Misako, Shingai Masashi, Seya Tsukasa

Molecular immunology ( Pergamon-elsevier science ltd )  57 ( 2 ) 100 - 109   2014年

Measles virus (MV) infects CD150Tg/ifnar (IFN alpha receptor)(-/-) mice but not CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow-derived dendritic cells (BMDCs) from CD150Tg/Ifnar(-/-) mice are permissive to MV in contrast to those from simple CD150Tg mice, which reveals a crucial role of type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA virus infection usually allows cells to generate double-stranded RNA and induce activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to the production of type I IFN through the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found CD150Tg/Mavs(-/-)BMDCs, but not CD150Tg/Irf3(-/-)/Irf7-/-BMDCs, permissive to MV. IFN-alpha/beta were not induced in MV-infected CD150Tg/Mavs--/-BMDCs, while IFN-13 was subtly induced in CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs. In vivo systemic infection was therefore established by transfer of MV-infected CD150Tg/Mavs-/- BMDCs to CD150Tg//fnar-/- mice. These data indicate that MAVS-dependent, IRF3/7-independent IFN-13 induction triggers the activation of the IFNAR pathway so as to restrict the spread of MV by infected BMDCs. Hence, MAVS participates in the initial induction of type I IFN in BMDCs and IFNAR protects against MV spreading. We also showed the importance of IL-10-producing CD4+ T cells induced by MV-infected BMDCs in vitro, which may account for immune modulation due to the functional aberration of DCs. (C) 2013 Elsevier Ltd. All rights reserved.

DOI

INAMはIFNγ誘導を引き起こす迅速なNKアクセサリー細胞の相互作用に重要な役割を担っている(INAM plays a critical role in rapid NK-accessory cell interaction leading to IFN γ induction)

Kasamatsu Jun, Oshiumi Hiroyuki, Ebihara Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  42 ( Proceedings ) 83 - 83   2013年11月

誘導性MHCクラスI発現で明らかとなった、MHCクラスI(MHC-I)とLy49受容体のトランス相互作用を介したNK細胞のライセンシング(教育)(NK cell licensing(education) through Ly49 receptor trans-interactions with MHC class I(MHC-I) as revealed by inducible MHC-I expression)

Ebihara Takashi, Jonsson A. Helena, Yokoyama M. Wayne

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  42 ( Proceedings ) 82 - 82   2013年11月

生体内においてIRF-3-dependent NK-activating moleculeはNK細胞の活性化を制御する

笠松純, 押海裕之, 海老原敬, 松本美佐子, 瀬谷司

日本生体防御学会学術総会講演抄録集   24th   2013年

J-GLOBAL

Cross-priming for antitumor ctl induced by soluble ag + polyi: C depends on the ticam-1 pathway in mouse cd11c+/CD8α+ dendritic cells

Azuma, M., Ebihara, T., Oshiumi, H., Matsumoto, M., Seya, T.

OncoImmunology   1 ( 5 )   2012年

DOI

樹状細胞・マクロファージによる免疫応答調節と免疫病態との関連 マウスAg提示細胞においてPolyI:C誘発性交差プライミングと抗腫瘍CTLはTICAM-1経路に依存する(PolyI:C-induced cross-priming and antitumor CTL depends on the TICAM-1 pathway in mouse Ag-presenting cells)

Azuma Masahiro, Ebihara Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  40   198 - 198   2011年11月

Pattern recognition receptors of innate immunity and their application to tumor immunotherapy

Tsukasa Seya, Hiroaki Shime, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto

Cancer Science ( Wiley )  101 ( 2 ) 313 - 320   2010年02月

DOI

Dendritic cell-derived TNF-α is responsible for development of IL-10-producing CD4+ T cells

Hirata Noriyuki, Yanagawa Yoshiki, Satoh Masashi, Ogura Hisako, Ebihara Takashi, Noguchi Masayuki, Matsumoto Machiko, Togashi Hiroko, Seya Tsukasa, Onoé Kazunori, Iwabuchi Kazuya

Cellular Immunology ( Elsevier )  261 ( 1 ) 37 - 41   2010年

Immature dendritic cells (DCs) appear to be involved in peripheral immune tolerance via induction of IL-10-producing CD4+ T cells. We examined the role of TNF-α in generation of the IL-10-producing CD4+ T cells by immature DCs. Immature bone marrow-derived DCs from wild type (WT) or TNF-α^[-/-] mice were cocultured with CD4+ T cells from OVA specific TCR transgenic mice (OT-II) in the presence of OVA_[323-339] peptide. The WT DCs efficiently induced the antigen-specific IL-10-producing CD4+ T cells, while the ability of the TNF-α^[-/-] DCs to induce these CD4+ T cells was considerably depressed. Addition of exogenous TNF-α recovered the impaired ability of the TNF-α^[-/-] DCs to induce IL-10-producing T cells. However, no difference in this ability was observed between TNF-α^[-/-] and WT DCs after their maturation by LPS. Thus, TNF-α appears to be critical for the generation of IL-10-producing CD4+ T cells during the antigen presentation by immature DCs.

DOI

IL-6 and IFN-α from dsRNA-stimulated dendritic cells control expansion of regulatory T cells

Kubota Nobuhiko, Ebihara Takashi, Matsumoto Misako, Gando Satoshi, Seya Tsukasa

Biochemical and Biophysical Research Communications ( Elsevier )  391 ( 3 ) 1421 - 1426   2010年

Foxp3+CD4+ regulatory T cells (Treg) control not only autoinimunity but also the effective immune response against RNA virus infections, which produces virus-derived double-stranded RNA (dsRNA). To induce effective anti-viral immunity, it is a key issue to learn how Treg respond to dsRNA in vitro and in vivo. We here showed that synthetic dsRNA, polyI:C, caused peripheral expansion of functional Treg in a TICAM-1- and IL-6-dependent manner in vivo. PolyI:C did not expand Treg directly, but promoted the expansion of naturally occurring Treg indirectly through IL-6 produced from dendritic cells (DCs). In addition, the expansion of Treg by IL-6 was inhibited by IFN-α from polyI:C-stimulated DCs. These data suggest that the balance of IL-6 and IFN-α in the region of RNA virus infection may determine the number of peripheral Treg, which affects the effective immune responses against viruses.

DOI

The peptide sequence of diacyl lipopeptides determines dendritic cell TLR2-mediated NK activation

Azuma, M., Sawahata, R., Akao, Y., Ebihara, T., Yamazaki, S., Matsumoto, M., Hashimoto, M., Fukase, K., Fujimoto, Y., Seya, T.

PLoS ONE   5 ( 9 )   2010年

Natural killer (NK) cells are lymphocyte effectors that are activated to control certain microbial infections and tumors. Many NK-activating and regulating receptors are involved in regulating NK cell function. In addition, activation of naïve NK cells is fundamentally triggered by cytokines or myeloid dendritic cells (mDC) in various modes. In this study, we synthesized 16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2Cys) lipopeptides with sequences designed from lipoproteins of Staphylococcus aureus, and assessed their functional properties using mouse (C57BL/6) bone marrow-derived DC (BMDC) and NK cells. NK cell activation was evaluated by three criteria: IFN-gamma production, up-regulation of NK activation markers and cytokines, and NK target (B16D8 cell) cytotoxicity. The diacylated lipopeptides acted as TLR2 ligands, inducing up-regulation of CD25/CD69/CD86, IL-6, and IL-12p40, which represent maturation of BMDC. Strikingly, the Pam2Cys lipopeptides induced mouse NK cell activation based on these criteria. Cell-cell contact by Pam2Cys peptide-stimulated BMDC and NK cells rather than soluble mediators released by stimulated BMDC induced activation of NK cells. For most lipopeptides, the BMDC TLR2/MyD88 pathway was responsible for driving NK activation, while some slightly induced direct activation of NK cells via the TLR2/MyD88 pathway in NK cells. The potential for NK activation was critically regulated by the peptide primary sequence. Hydrophobic or proline-containing sequences proximal to the N-terminal lipid moiety interfered with the ability of lipopeptides to induce BMDC-mediated NK activation. This mode of NK activation is distinctly different from that induced by polyI:C, which is closely associated with type I IFN-inducing pathways of BMDC. These results imply that the MyD88 pathway of BMDC governs an alternative NK-activating pathway in which the peptide sequence of TLR2-agonistic lipopeptides critically affects the potential for NK activation.

DOI PubMed

樹状細胞における細胞内シグナル伝達とその意義 骨髄由来樹状細胞におけるTLR3/TICAM-1経路を介したクロスプレゼンテーションの制御(Regulation of cross-presentation through the TLR3/TICAM-1 pathway in mDC)

Azuma Masahiro, Ebihara Takashi, Kubota Nobuhiko, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  39   181 - 181   2009年11月

Dendritic Cell/NK Cell Interaction in RNA Virus Infection

Takashi Ebihara, Misako Matsumoto, Tsukasa Seya

Current Immunology Reviews ( Bentham Science Publishers Ltd. )  5 ( 3 ) 200 - 207   2009年08月

DOI

Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice

Yuusuke Akao, Takashi Ebihara, Hisayo Masuda, Yoshiko Saeki, Takashi Akazawa, Kaoru Hazeki, Osamu Hazeki, Misako Matsumoto, Tsukasa Seya

Cancer Science ( Wiley )  100 ( 8 ) 1494 - 1501   2009年08月

Oral administration of hot-water extract of Spirulina, cyanobacterium Spirulina platensis, leads to augmentation of NK cytotoxicity in humans. Here, we applied to syngeneic tumor-implant mice (C57BL/6 versus B16 melanoma) Spirulina to elucidate the mechanism of raising antitumor NK activation. A B16D8 subcell line barely expressed MHC class I but about 50% expressed Rae-1, a ligand for NK activation receptor NKG2D. The Rae-1-positive population of implant B16 melanoma was effectively eliminated in the tumor mass progressed in mice. This antitumor activity was induced in parallel with IFN-gamma and abolished in mice by treatment with asialoGM-1 but not CD8beta Ab, suggesting the effector is NK cell. NK cell activation occurred in the spleen of wild-type mice medicated with Spirulina. This Spirulina-mediated enhanced NK activation was abrogated in MyD88 -/- mice but not in TICAM-1 -/- mice. The NK activating properties of Spirulina depending on MyD88 were confirmed with in vitro bone marrow-derived dendritic cells expressing TLR2/4. In D16D8 tumor challenge studies, the antitumor effect of Spirulina was abolished in MyD88 -/- mice. Hence, orally administered Spirulina enhances tumoricidal NK activation through the MyD88 pathway. Spirulina exerted a synergistic antitumor activity with BCG-cell wall skeleton, which is known to activate the MyD88 pathway via TLR2/4 with no NK enhancing activity. Spirulina and BCG-cell wall skeleton synergistically augmented IFN-gamma production and antitumor potential in the B16D8 versus C57BL/6 system. We infer from these results that NK activation by Spirulina has some advantage in combinational use with BCG-cell wall skeleton for developing adjuvant-based antitumor immunotherapy.

DOI PubMed

Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3

Iwakiri Dai, Zhou Li, Samanta Mrinal, Matsumoto Misako, Ebihara Takashi, Seya Tsukasa, Imai Shosuke, Fujieda Mikiya, Kawa Keisei, Takada Kenzo

Journal of Experimental Medicine ( Rockefeller University Press )  206 ( 10 ) 2091 - 2099   2009年08月

Epstein-Barr virus-encoded small RNA (EBER) is nonpolyadenylated, noncoding RNA that forms stem-loop structure by intermolecular base-pairing, giving rise to double-stranded RNA (dsRNA)-like molecules, and exists abundantly in EBV-infected cells. Here, we report that EBER induces signaling from the Toll-like receptor 3 (TLR3), which is a sensor of viral double-stranded RNA (dsRNA) and induces type I IFN and proinflammatory cytokines. A substantial amount of EBER, which was sufficient to induce signaling from TLR3, was released from EBV-infected cells, and the majority of the released EBER existed as a complex with a cellular EBER-binding protein La, suggesting that EBER was released from the cells by active secretion of La. Sera from patients with infectious mononucleosis (IM), chronic active EBV infection (CAEBV), and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), whose general symptoms are caused by proinflammatory cytokines contained EBER, and addition of RNA purified from the sera into culture medium induced signaling from TLR3 in EBV-transformed lymphocytes and peripheral mononuclear cells. Furthermore, DCs treated with EBER showed mature phenotype and antigen presentation capacity. These findings suggest that EBER, which is released from EBV-infected cells, is responsible for immune activation by EBV, inducing type I IFN and proinflammatory cytokines. EBER-induced activation of innate immunity would account for immunopathologic diseases caused by active EBV infection.

DOI

樹状細胞TLR3の誘導するNK細胞活性化の分子機構

海老原 敬, 松本 美佐子, 瀬谷 司

補体シンポジウム講演集 ( (一社)日本補体学会 )  46   32 - 33   2009年08月

Functional evolution of the TICAM-1 pathway for extrinsic RNA sensing

Seya, T., Matsumoto, M., Ebihara, T., Oshiumi, H.

Immunological Reviews ( Wiley )  227 ( 1 ) 44 - 53   2009年

DOI

抗腫瘍エフェクター機構とその制御 Spirulina熱水抽出物経口投与による抗腫瘍NK細胞の活性化(Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice)

Akao Yusuke, Ebihara Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  38   112 - 112   2008年11月

樹状細胞機能を制御する分子基盤 マウス樹状細胞からのIL-10産生におけるTLR4とTLR2との相乗作用(TLR4 acts in synergy with TLR2 in IL-10 production by murine dendritic cells)

Hirata Noriyuki, Yanagawa Yoshiki, Ebihara Takashi, Seya Tsukasa, Uematsu Satoshi, Akira Shizuo, Hayashi Fumie, Iwabuchi Kazuya, Onoe Kazunori

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  38   124 - 124   2008年11月

特殊なリンパ球 NK細胞や他のリンパ球 樹状細胞における新規NK活性化分子の解析(An analysis of new NK-activating molecules on myloid DC)

Ebihara Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  38   73 - 73   2008年11月

腫瘍抗原および樹状細胞 樹状細胞におけるTLR3/TICAM-1経路を介したクロスプレゼンテーションの制御(Regulation of dendritic coll cross-presentation induced through the TLR3/TICAM-1 pathway)

Azuma Masahiro, Ebihara Takashi, Kubota Nobuhiko, Akazawa Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  38   105 - 105   2008年11月

DDX3ヘリケースはRIG-I/IPS-1経路への参加因子で1型インターフェロン誘導を助長する(DDX3 helicase assembles in the RIG-I/IPS-1 pathway to enhance IFN-beta induction)

押海 裕之, 松本 美佐子, 海老原 敬, 瀬谷 司

日本癌学会総会記事 ( (一社)日本癌学会 )  67回   107 - 107   2008年09月

スピルリナ経口投与によるがん退縮のメカニズム(Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice)

瀬谷 司, 海老原 敬, 志馬 寛明, 押海 裕之, 赤尾 雄介, 松本 美佐子

日本癌学会総会記事 ( (一社)日本癌学会 )  67回   273 - 273   2008年09月

Spirulina熱水抽出物経口投与による抗腫瘍NK細胞の活性化

赤尾 雄介, 海老原 敬, 松本 美佐子, 瀬谷 司

補体シンポジウム講演集 ( (一社)日本補体学会 )  45   146 - 146   2008年07月

TICAM1依存性クロスプレゼンテーションの解析

東 正大, 海老原 敬, 松本 美佐子, 瀬谷 司

補体シンポジウム講演集 ( (一社)日本補体学会 )  45   135 - 135   2008年07月

抗HCV樹状細胞応答の解析

海老原 敬, 松本 美佐子, 脇田 隆字, 瀬谷 司

補体シンポジウム講演集 ( (一社)日本補体学会 )  45   1316 - 1316   2008年07月

【自然免疫とウイルス感染】HCVと自然免疫

海老原 敬, 松本 美佐子, 瀬谷 司

ウイルス ( 日本ウイルス学会 )  58 ( 1 ) 19 - 26   2008年06月

C型肝炎ウイルス（HCV）感染症は高率に慢性化すること，その結果，肝硬変・肝癌を発症しうることにその特徴がある．高率に慢性化する原因としては，ウイルス側の要因と宿主側の要因があるとされてきた．特に宿主側の要因として，HCVに対する免疫反応（特にCTLやNK細胞活性）が弱いことと感染の慢性化には相関があるといわれている．中でも自然免疫反応の起点である樹状細胞についての報告は多く，HCVの樹状細胞への感染により機能が阻害されている可能性が示唆されている．しかし，相矛盾する報告もあり現在まで一致した見解には至っていない．2005年脇田らにより<I>in vitro</I>でHCVの培養（JFH1株）が可能になり，<I>in vitro</I>での自然免疫応答の解析が可能になった．本総説ではHCVによる自然免疫制御について現在までの知見を概説するとともにJFH1株を用いた樹状細胞応答について紹介する．

DOI

TLR4とTLR2を介して刺激された樹状細胞における選択的かつ相乗的な抗炎症性サイトカインの産生

平田 徳幸, 柳川 芳毅, 海老原 敬, 瀬谷 司, 植松 智, 審良 静男, 林 史恵, 岩渕 和也, 小野江 和則

日本リンパ網内系学会会誌 ( (一社)日本リンパ網内系学会 )  48   103 - 103   2008年05月

J-GLOBAL

Detection of four genetic subgroup-specific antibodies to human metapneumovirus attachment (G) protein in human serum

Endo, R., Ebihara, T., Ishiguro, N., Teramoto, S., Ariga, T., Sakata, C., Hayashi, A., Ishiko, H., Kikuta, H.

Journal of General Virology   89 ( 8 )   2008年

DOI

Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells

Hirata, N., Yanagawa, Y., Ebihara, T., Seya, T., Uematsu, S., Akira, S., Hayashi, F., Iwabuchi, K., Onoé, K.

Molecular Immunology   45 ( 10 )   2008年

DOI

Soluble G protein of respiratory syncytial virus inhibits Toll-like receptor 3/4-mediated IFN-beta induction

Shingai, M., Azuma, M., Ebihara, T., Sasai, M., Funami, K., Ayata, M., Ogura, H., Tsutsumi, H., Matsumoto, M., Seya, T.

International Immunology   20 ( 9 ) 1169 - 1180   2008年

Monocyte-derived dendritic cells (mDCs) recognize viral RNA extrinsically by Toll-like receptor (TLR) 3 on the membrane and intrinsically retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm to induce type I IFNs and mDC maturation. When mDCs were treated with live or UV-irradiated respiratory syncytial virus (RSV), early (∼4 h) induction of IFN-β usually occurs in other virus infections was barely observed. Live RSV subsequently replicated to activate the cytoplasmic IFN-inducing pathway leading to robust type I IFN induction. We found that RSV initial attachment to cells blocked polyI:C-mediated IFN-β induction, and this early IFN-β-modulating event was abrogated by antibodies against envelope proteins of RSV, demonstrating the presence of a IFN-regulatory mode by early RSV attachment to host cells. By IFN-stimulated response element (ISRE) reporter analysis in HEK293 cells, polyI:C- or LPS-mediated ISRE activation was dose dependently inhibited by live and inactive RSV to a similar extent. Of the RSV envelope proteins, simultaneously expressed or exogenously added RSV G or soluble G (sG) proteins inhibited TLR3/4-mediated ISRE activation in HEK293 cells. sG proteins expressed in cells did not affect the RIG-I/MDA5 pathway but inhibited the TLR adaptor TRIF/TICAM-1 pathway for ISRE activation. Finally, extrinsically added sG protein suppressed the production of IFN-β in mDCs. Although the molecular mechanism of this extrinsic functional mode of the RSV G glycoprotein (G protein) remains undetermined, G proteins may neutralize the fusion glycoprotein function that promotes IFN-mediated mDC modulation via TLR4 and may cause insufficient raising cell-mediated immunity against RSV. © The Japanese Society for Immunology. 2008. All rights reserved.

DOI PubMed

HCV粒子ではなくHCV感染アポトーシス細胞は樹状細胞を制御し、T細胞とNK細胞を活性化する(HCV-infected apoptotic cells,but not HCV particles,modulate dendritic cell function to activate T cells and NK cells)

Ebihara Takashi, Matsumoto Misako, Wakita Takaji, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  37   76 - 76   2007年10月

TLR3/TICAM1を介した制御性T細胞の増殖についての検討(An expansion of regulatory T cells via TLR3/TICAM1 (TRIF) signal)

久保田 信彦, 海老原 敬, 東 正広, 松本 美佐子, 丸藤 哲, 瀬谷 司

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  37   60 - 60   2007年10月

【最近のウイルス感染症の話題】小児呼吸器感染症とコロナウイルス

海老原 敬, 瀬谷 司, 菊田 英明

小児科 ( 金原出版(株) )  48 ( 10 ) 1403 - 1409   2007年09月

TLR3/TICAM-1(TRIF)シグナルを介したI型IFN非依存性抗腫瘍NK細胞活性(Type I IFN-independent anti-tumor NK cell activation via TLR3/TICAM-1 (TRIF) signal)

海老原 敬, 赤澤 隆, 井上 徳光, 松本 美佐子, 瀬谷 司

日本癌学会総会記事 ( (一社)日本癌学会 )  66回   41 - 41   2007年08月

TLRアダプター過剰発現樹状細胞の調製とがん治療への応用(Application of TLR adaptor over-expressing DC to cancer immunotherapy)

赤澤 隆, 海老原 敬, 井上 徳光, 松本 美佐子, 瀬谷 司

日本癌学会総会記事 ( (一社)日本癌学会 )  66回   41 - 41   2007年08月

Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors

Takashi Akazawa, Masashi Shingai, Miwa Sasai, Takashi Ebihara, Norimitsu Inoue, Misako Matsumoto, Tsukasa Seya

FEBS Letters ( Wiley )  581 ( 18 ) 3334 - 3340   2007年06月

Myeloid dendritic cells (mDCs) play an important role in the initiation of immune responses to cancer and infectious diseases. Toll-like receptors (TLRs) expressed on mDCs recognize microbial products to elicit signals for mDC maturation, including cytokine production, antigen-presentation and induction of effector cells. TLR agonists work as adjuvants to modulate the function of mDCs. In TLR signaling, MyD88 and TRIF/TICAM-1 are major TLR adaptor molecules, which when overexpressed are able to transduce downstream signals without TLR stimuli. We successfully introduced the adaptors into mouse bone marrowderived mDCs using lentiviral vectors. Introduction of MyD88 into mDCs in vitro led to the production of IL-6 and IL-12p40 while introduction of TICAM-1 stimulated interferon (IFN)-alpha production. Expression of TICAM-1, but not MyD88, in mDCs slightly induced the co-stimulatory molecule CD86, while significant upregulation of CD86 was observed in response to other TLR stimuli. Both MyD88 and TICAM-1 augmented allogeneic mixed lymphocyte reaction (MLR). Ex vivo mouse spleen cells pre-exposed to tumor antigen exhibited antitumor cytotoxicity when incubated with MyD88- or TICAM-1-expressing mDCs. Using mDC adoptive transfer and a syngeneic mouse tumor implant model, we established an antitumor immunotherapy whereby tumor growth is retarded by adaptor-manipulated mDCs. © 2007 Federation of European Biochemical Societies.

DOI PubMed

TLR3/TICAM-1(TRIF)シグナルを介したNK細胞による抗腫瘍免疫

海老原 敬, 赤澤 隆, 瀬谷 司

基盤的癌免疫研究会総会抄録 ( 日本がん免疫学会 )  11回   37 - 37   2007年05月

臨床応用の期待される基礎研究 抗腫瘍NK活性化誘導のための代替的免疫療法(Alternative immunotherapy for inducing antitumor NK activation)

Seya Tsukasa, Akazawa Takashi, Ebihara Takashi, Inoue Norimitsu, Matsumoto Misako

基盤的癌免疫研究会総会抄録 ( 日本がん免疫学会 )  11回   29 - 29   2007年05月

がんのアジュバント免疫療法の確立と開発

瀬谷 司, 松本 美佐子, 海老原 敬, 赤沢 隆

日本気管食道科学会会報 ( (NPO)日本気管食道科学会 )  58 ( 2 ) 85 - 95   2007年04月

Toll様受容体(TLR)は樹状細胞にレパトアで発現し、微生物成分を認識して転写因子NF-κBやIRF-3を活性化する。樹状細胞応答としてサイトカインとI型interferon(IFN)を誘導する。また、TLR刺激は樹状細胞を成熟化に導き、CTL,NKの活性化を誘起する。TLRによるこれらのエフェクター誘導の機序は不明である。マウス移植がんの系を用いるとCTL,NK依存性の抗がん免疫活性を分別測定できる。われわれはTLR2/4をBCG-CWSで刺激することでMyD88アダプター依存性にCTLが誘導されること、TLR3をpolyI:Cで刺激することでTICAM-1依存性にNKが誘導されることを本研究で明らかにした。この応答には樹状細胞のTLR-アダプター経路が重要である。樹状細胞がアジュバント要求性にさまざまな成熟化模様を呈するのはTLRのシグナル経路に依存することと推定される。毒性の少ない誘導体の開発が望ましいが、BCG-CWS,polyI:Cは樹状細胞療法のアジュバントとして抗がん免疫療法などの臨床応用に有用である。(著者抄録)

Development of a Rapid Chromatographic Immunoassay for Detection of Human Metapneumovirus Using Monoclonal Antibodies Against Nucleoprotein of hMPV

Hideaki Kikuta, Takashi Ebihara, Rika Endo, Nobuhisa Ishiguro, Chikako Sakata, Susumu Ochiai, Hiroaki Ishiko, Reiko Gamo, Takashi Sato

Hybridoma ( Mary Ann Liebert Inc )  26 ( 1 ) 17 - 21   2007年02月

DOI

Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells

Akazawa, T., Ebihara, T., Okuno, M., Okuda, Y., Shingai, M., Tsujimura, K., Takahashi, T., Ikawa, M., Okabe, M., Inoue, N., Okamoto-Tanaka, M., Ishizaki, H., Miyoshi, J., Matsumoto, M., Seya, T.

Proceedings of the National Academy of Sciences of the United States of America   104 ( 1 ) 252 - 257   2007年

Myeloid dendritic cells (mDCs) recognize and respond to polyl:C, an analog of dsRNA, by endosomal Toll-like receptor (TLR) 3 and cytoplasmic receptors. Natural killer (NK) cells are activated in vivo by the administration of polyl:C to mice and in vitro are reciprocally activated by mDCs, although the molecular mechanisms are as yet undetermined. Here, we show that the TLR adaptor TICAM-1 (TRIF) participates in mDC-derived antitumor NK activation. In a syngeneic mouse tumor implant model (CS7BL/6 vs. B16 melanoma with low H-2 expresser), i.p. administration of polyl:C led to the retardation of tumor growth, an effect relied on by NK activation. This NK-dependent tumor regression did not occur in TICAM-1-/- or IFNAR-/- mice, whereas a normal NK antitumor response was induced in PKR-/-, MyD88-/-, IFN-β-/-, and wild-type mice. IFNAR was a prerequisite for the induction of IFN-α/β and TLR3. The lack of TICAM-1 did not affect IFN production but resulted in unresponsiveness to IL-12 production, mDC maturation, and polyl:C-mediated NK-antitumor activity. This NK activation required NK-mDC contact but not IL-12 function in in vitro transwell analysis. Implanted tumor growth in IFNAR-/- mice was retarded by adoptively transferring polyl:C-treated TICACM-1-positive mDCs but not TICAM-1 -/- mDCs. Thus, TICAM-1 in mDCs critically facilitated mDC-NK contact and activation of antitumor NK, resulting in the regression of low MHC-expressing tumors. © 2006 by The National Academy of Sciences of the USA.

DOI PubMed

Basic Studies on the Development of Adjuvant Immunotherapy

Tsukasa Seya, Misako Matsumoto, Takashi Ebihara, Takashi Akazawa

Nihon Kikan Shokudoka Gakkai Kaiho ( Japan Broncho-Esophagological Society )  58 ( 2 ) 85 - 95   2007年

DOI

Differential type I IFN-inducing abilities of wild-type versus vaccine strains of measles virus

Shingai, M., Ebihara, T., Begum, N.A., Kato, A., Honma, T., Matsumoto, K., Saito, H., Ogura, H., Matsumoto, M., Seya, T.

Journal of Immunology   179 ( 9 )   2007年

DOI

NK-Activating dendritic cells are elicited by stimulation with toll-like receptor 3

Seya, T., Matsumoto, M., Ebihara, T., Akazawa, T.

Hirosaki Medical Journal   59 ( SUPPL. )   2007年

Recombinant interleukin-12 and interleukin-18 antitumor therapy in a guinea-pig hepatoma cell implant model

Shiratori, I., Suzuki, Y., Oshiumi, H., Begum, N.A., Ebihara, T., Matsumoto, M., Hazeki, K., Kodama, K., Kashiwazaki, Y., Seya, T.

Cancer Science   98 ( 12 ) 1936 - 42   2007年

Interleukin (IL)-12 and IL-18 are secreted by myeloid cells activated with adjuvants such as Bacillus Calmette-Guérin (BCG) cell wall. They induce T-helper 1 polarization in the host immune system and upregulate production of lymphocyte interferon-gamma, which leads to the induction of an antitumor gene program. It has been reported that humans have an immune system that more closely resembles that of the guinea pig in adjuvant-response features rather than the mouse system, which prevents the mouse results being extrapolated to human immunotherapy. Here we have constructed a tumor-implant system in guinea pigs to evaluate the antitumor potential of guinea pig IL-12 (gpIL-12) and guinea pig IL-18 (gpIL-18). Purified recombinant gpIL-12 and gpIL-18 were prepared and applied intraperitoneally to tumor-bearing (line 10 hepatoma) guinea pigs as the basis of the adjuvant immunotherapy. Intraperitoneal administration of gpIL-12 and gpIL-18 led to retardation of primary tumor growth and suppression of lymph-node metastasis in tumor-bearing guinea pigs. The permissible range of IL-12 appeared wider in guinea pigs than in mice. Even at an IL-12 dose higher than that in mice, there was no evidence of side-effects until day 26, when the guinea pigs were killed. gpIL-18 augmented the antitumor effect of gpIL-12 but exerted less ability to suppress lymph-node metastasis. The effects of gpIL-12 and gpIL-18 on the tumors implanted in guinea pigs will encourage us to use IL-12- and IL-18-inducible adjuvants for immunotherapy in human patients with solid cancer.

DOI PubMed

Seroepidemiology of Human Bocavirus in Hokkaido Prefecture, Japan

Endo Rika, Ishiguro Nobuhisa, Kikuta Hideaki, Teramoto Shinobu, Shirkoohi Reza, Ma Xiaoming, Ebihara Takashi, Ishiko Hiroaki, Ariga Tadashi

Journal of Clinical Microbiology ( American Society for Microbiology )  45 ( 10 ) 3218 - 3223   2007年

A new human virus, provisionally named human bocavirus (HBoV), was discovered by Swedish researchers in 2005. A new immunofluorescence assay using Trichoplusia ni insect cells infected with a recombinant baculovirus expressing the VP1 protein of HBoV was developed, and the levels of immunoglobulin G antibody to the VP1 protein of HBoV in serum samples were measured. The overall seroprevalence rate of antibodies against the VP1 protein of HBoV in a Japanese population aged from 0 months to 41 years was 71.1% (145 of 204). The seropositive rate was lowest in the age group of 6 to 8 months and gradually increased with age. All of the children had been exposed to HBoV by the age of 6 years. A rise in titers of antibody against the VP1 protein of HBoV during the convalescent phase was observed for four patients with lower respiratory tract infections, and HBoV DNA was detected in nasopharyngeal swab and serum samples from all four patients. These results suggest that HBoV is a ubiquitous virus acquired early in life and that HBoV might play a role in the course of lower respiratory tract infections.

DOI

NK-Activating Dendritic Cells Are Elicited by Stimulation with Toll-Like Receptor 3. [Emerging Theories of Host Defense. The 10th Meeting Hirosaki International Forum of Medical Science. Communication Center Hirosaki University School of Medicine. Hirosaki on November 21-22, 2006]

Seya Tsukasa, Matsumoto Misako, Ebihara Takashi, Akazawa Takashi

弘前醫學 ( 弘前大学 )  59   S43 - S51   2007年

Double-stranded （ds）RNA-recognition receptors reside in the cytoplasm and membranes of cells. Thesereceptors are implicated in the differential screening of microbes by the host. Myeloid dendritic cells （mDCs）recognize and respond to polyI:C, an analog of dsRNA, by endosomal TLR3 and cytoplasmic MDA5. NK cells areinduced in vivo by the administration of polyI:C to mice and in vitro are reciprocally activated by mDCs, although themolecular mechanisms as yet undetermined. Here, we show that the TLR adapter TICAM-1 （TRIF） participates inmDC-derived antitumor NK activation. In a syngeneic mouse tumor implant model, intraperitoneal administration ofpolyI:C led to the retardation of tumor growth, which eff ect relied largely on NK activation. This NK-dependent tumorregression did not occur in TICAM-1-/- or IFNAR-/- mice, while a normal NK antitumor response was induced in PKR-/-,MyD88-/-, IFN-β-/- and wild-type mice. IFNAR was a prerequisite for the induction of IFN-α/β and TLR3. The lackof TICAM-1 did not aff ect IFN production but resulted in unresponsiveness to IL-12 production, mDC maturation andpolyI:C-mediated antitumor activity. This NK activation required NK-mDC contact in in vitro transwell analysis. NKantitumoractivity was successfully introduced into tumor-implanted mice by transferring mDCs expressing TICAM-1.Implanted tumor growth in IFNAR-/- mice was retarded by adoptively transferring polyI:C-treated TICACM-1-positivemDCs but not TICAM-1-/- mDCs. Thus, TICAM-1 rather than MDA5 in mDCs critically facilitated mDC-NK contactand activation of antitumor NK, resulting in the regression of low MHC-expressing tumors

NK細胞とMHC受容体 TLRリガンド刺激及びRNAウイルス感染によるヒト樹状細胞上のNKG2Dリガンドの誘導(NKG2D ligands are induced on human dendritic cells by TLR ligand stimulation and RNA virus infection)

Ebihara Takashi, Shingai Masashi, Akazawa Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  36   253 - 253   2006年11月

ウイルス感染と宿主応答・宿主側の要因 感染樹状細胞における麻疹ウイルスによるI型IFN誘導メカニズム(A mechanism by which measles virus induces Type-I IFN in infected dendritic cells)

Shingai Masashi, Ebihara Takashi, Matsumoto Misako, Seya Tsukasa

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  36   207 - 207   2006年11月

小児の下気道感染症患者からのヒトボカウイルス(Human Bocavirus)の検出

石黒 信久, 遠藤 理香, 石古 博昭, 菊田 英明, 馬 暁明, 海老原 敬

感染症学雑誌 ( (一社)日本感染症学会 )  80 ( 6 ) 742 - 742   2006年11月

小児human metapneumovirusおよびrespiratory syncytial virus感染症の臨床像の比較

高橋 豊, 羽田 美保, 米川 元晴, 田端 祐一, 鹿野 高明, 海老原 敬, 遠藤 理香, 石黒 信久, 菊田 英明

小児科 ( 金原出版(株) )  47 ( 7 ) 1115 - 1120   2006年06月

human metapneumovirus(hMPV)感染症とrespiratory syncytial virus(RSV)感染症を比較した論文をレビューするとともに,入院症例についても検討した.対象はhMPV感染症患児が38例,RSV感染症は2001年と2002年の2年間に入院加療した215例であった.1)hMPV感染症は発熱症例の比率が高く,有熱期間がなく,また喘鳴を呈する比率が高かった.更に血小板数が少なく,血清LDHが低かった.2)レビューした報告では,hMPV感染症はRSV感染症より呼吸器症状の程度が軽いことが示されていたが,今回の調査では明らかにならなかった

小児の下気道感染症患者からのヒトボカウイルス(Human Bocavirus)の検出

石黒 信久, 遠藤 理香, 石古 博昭, 菊田 英明, 馬 暁明, 海老原 敬

感染症学雑誌 ( (一社)日本感染症学会 )  80 ( 臨増 ) 248 - 248   2006年03月

Detection of antibodies against human metapneumovirus by western blot using recombinant nucleocapsid and matrix proteins

Nobuhisa Ishiguro, Takashi Ebihara, Rika Endo, Xiaoming Ma, Eri Kawai, Hiroaki Ishiko, Hideaki Kikuta

Journal of Medical Virology ( Wiley )  78 ( 8 ) 1091 - 1095   2006年

DOI

Detection of human bocavirus in Japanese children with lower respiratory tract infections

Ma Xiaoming, Endo RIka, Ishiguro Nobuhisa, Ebihara Takashi, Ishiko Hiroaki, Ariga Tadashi, Kikuta Hideaki

Journal of Clinical Microbiology ( American Society of Microbiology )  44 ( 3 ) 1132 - 1134   2006年

Human bocavirus (HBoV), a newly cloned human virus of the genus Bocavirus, was detected by PCR from nasopharyngeal swab samples collected from children with lower respiratory tract infections (8 of 318, 5.7%). HBoV may be one of the causative agents of lower respiratory tract infections in young children. (48 words)

DOI

樹状細胞におけるULBPの発現とTLRシグナルによる発現上昇誘導

海老原 敬, 赤澤 隆, 松本 美佐子, 瀬谷 司

日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 )  35   103 - 103   2005年11月

Production and Characterization of Neutralizing Monoclonal Antibodies Against Human Metapneumovirus F Protein

Xiaoming Ma, Rika Endo, Takashi Ebihara, Nobuhisa Ishiguro, Hiroaki Ishiko, Hideaki Kikuta

Hybridoma ( Mary Ann Liebert Inc )  24 ( 4 ) 201 - 205   2005年08月

DOI

新たに発見された呼吸器感染症起因ウイルスであるヒト・メタニューモウイルスのG(attachment)蛋白塩基配列の多様性

石黒 信久, 遠藤 理香, 石古 博昭, 菊田 英明, 海老原 敬

感染症学雑誌 ( (一社)日本感染症学会 )  79 ( 8 ) 586 - 586   2005年08月

新しく発見されたhuman metapneumovirusに対する抗体の測定

海老原 敬, 遠藤 理香, 馬 暁明, 吉岡 幹朗, 石黒 信久, 菊田 英明

日本小児科学会雑誌 ( (公社)日本小児科学会 )  109 ( 7 ) 859 - 859   2005年07月

ラン藻類Spirulina抽出物の経口投与によるNK活性化とマウス移植がん退縮の検討

海老原 敬, 赤沢 隆, 増田 尚代, 松本 美佐子, 瀬谷 司

基盤的癌免疫研究会総会抄録 ( 日本がん免疫学会 )  9回   60 - 60   2005年06月

Differential gene expression of S100 protein family in leukocytes from patients with Kawasaki disease

Takashi Ebihara, Rika Endo, Hideaki Kikuta, Nobuhisa Ishiguro, Xiaoming Ma, Mitsunobu Shimazu, Takao Otoguro, Kunihiko Kobayashi

European Journal of Pediatrics ( Springer Nature )  164 ( 7 ) 427 - 431   2005年04月

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Human metapneumovirusが発作誘発に関与したと考えられた小児喘息患児の検討

高橋 豊, 佐藤 宏紀, 川原 朋乃, 藤原 ふみえ, 鹿野 高明, 海老原 敬, 石黒 信久, 菊田 英明

喘息 ( (株)メディカルレビュー社 )  18 ( 2 ) 77 - 80   2005年04月

Human metapneumovirus(hMPV)の小児喘息への関わりを検討するため,発作で受診した小児喘息患児のhMPVを検索し,陽性例の臨床的特徴について検討した.急性増悪で受診した小児喘息患児58例を対象とし,鼻汁検体のhMPVを検索した.58例中30例は38℃以上の発熱を認め,20例は入院加療となった.6例の鼻汁からhMPVを検出した.6例中4例はダニに対する特異IgE抗体が陽性で,アトピー型喘息と考えられた.6例中5例は39℃以上の高熱を伴い,4例は入院加療となっていた.白血球数増多は認めず,血清CRP値も,ほとんど増加せず,AST,LDH値も正常範囲である例が多かった.また,胸部レントゲン上肺炎を認めた症例もなかった

【日常よくみるウイルス感染症】ヒトメタニューモウイルス感染症の臨床像

海老原 敬, 菊田 英明

小児内科 ( (株)東京医学社 )  37 ( 1 ) 103 - 106   2005年01月

Detection of human coronavirus NL63 in young children with bronchiolitis

Takashi Ebihara, Rika Endo, Xiaoming Ma, Nobuhisa Ishiguro, Hideaki Kikuta

Journal of Medical Virology ( Wiley )  75 ( 3 ) 463 - 465   2005年

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Detection of human metapneumovirus antigens in nasopharyngeal secretions by an immunofluorescent-antibody test

Ebihara, T., Endo, R., Ma, X., Ishiguro, N., Kikuta, H.

Journal of Clinical Microbiology ( American Society for Microbiology )  43 ( 3 ) 1138 - 1141   2005年

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Immunofluorescence assay for detection of human metapneumovirus-specific antibodies by use of baculovirus-expressed fusion protein

Ishiguro, N., Ebihara, T., Endo, R., Ma, X., Shirotsuki, R., Ochiai, S., Ishiko, H., Kikuta, H.

Clinical and Diagnostic Laboratory Immunology   12 ( 1 )   2005年

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Lack of association between New Haven coronavirus and Kawasaki disease.

Ebihara, T., Endo, R., Ma, X., Ishiguro, N., Kikuta, H.

The Journal of infectious diseases ( Oxford University Press ({OUP}) )  192 ( 2 ) 351 - 352   2005年

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Questions concerning the New Haven coronavirus (multiple letters)

Van Der Hoek, L., Berkhout, B., Ebihara, T., Endo, R., Ma, X., Ishiguro, N., Kikuta, H., Belay, E.D., Erdman, D.D., Anderson, L.J., Peret, T.C.T., Schrag, S.J., Fields, B.S., Burns, J.C., Schonberger, L.B., Esper, F., Shapiro, E.D., Landry, M.L., Kahn, J.S., McIntosh, K.

Journal of Infectious Diseases   192 ( 2 )   2005年

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【呼吸器感染症2005】呼吸器感染症の診断と治療 ウイルス感染症 ヒト・メタニューモウイルス

海老原 敬, 菊田 英明

日本胸部臨床 ( 克誠堂出版(株) )  63 ( 増刊 ) S69 - S71   2004年11月

小児喘息発作誘発におけるHuman Metapneumovirusの関与についての検討

高橋 豊, 佐藤 宏紀, 川原 朋乃, 藤原 ふみえ, 鹿野 高明, 海老原 敬, 菊田 英明

日本小児アレルギー学会誌 ( (一社)日本小児アレルギー学会 )  18 ( 4 ) 486 - 486   2004年10月

EBウイルス(EBV)関連・非腫瘍性Tリンパ球増殖性疾患におけるEBV潜伏感染様式の検討

吉岡 幹朗, 石黒 信久, 海老原 敬, 遠藤 理香, 菊田 英明, 小林 邦彦

北海道医学雑誌 ( 北海道医学会 )  79 ( 4 ) 469 - 470   2004年07月

EBウイルス関連疾患におけるInternal ribosome entry site(IRES)領域の塩基配列の検討

遠藤 理香, 海老原 敬, 石黒 信久, 菊田 英明, 小林 邦彦

小児感染免疫 ( (一社)日本小児感染症学会 )  16 ( 1 ) 102 - 103   2004年04月

小児ヒトメタニューモウイルス感染症のウイルス学的,臨床学的検討

海老原 敬, 遠藤 理香, 石黒 信久, 菊田 英明, 小林 邦彦, 石古 博昭, 鈴木 英太郎, 原 三千丸, 高橋 豊

小児感染免疫 ( (一社)日本小児感染症学会 )  16 ( 1 ) 114 - 115   2004年04月

小児喘息発作誘発におけるHuman Metapneumovirusの関与

高橋 豊, 中村 明枝, 川原 朋乃, 藤原 ふみえ, 鹿野 高明, 海老原 敬, 菊田 英明

アレルギー ( (一社)日本アレルギー学会 )  53 ( 2-3 ) 312 - 312   2004年03月

Possible involvement in oncogenesis of a single base mutation in an internal ribosome entry site of Epstein–Barr nuclear antigen 1 mRNA

Rika Endo, Hideaki Kikuta, Takashi Ebihara, Nobuhisa Ishiguro, Kunihiko Kobayashi

Journal of Medical Virology ( Wiley )  72 ( 4 ) 630 - 634   2004年02月

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Clonal expansion of multiphenotypic Epstein–Barr virus-infected lymphocytes in chronic active Epstein–Barr virus infection

Rika Endo, Mikio Yoshioka, Takashi Ebihara, Nobuhisa Ishiguro, Hideaki Kikuta, Kunihiko Kobayashi

Medical Hypotheses ( Elsevier {BV} )  63 ( 4 ) 582 - 587   2004年01月

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Early reinfection with human metapneumovirus in an infant

EBIHARA T

J Clin Mirobiol ( American Society for Microbiology )  42 ( 12 ) 5944 - 5946   2004年

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High genetic diversity of the attachment (G) protein of human metapneumovirus

Ishiguro, N., Ebihara, T., Endo, R., Ma, X., Kikuta, H., Ishiko, H., Kobayashi, K.

Journal of Clinical Microbiology   42 ( 8 )   2004年

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Human metapneumovirus気道感染症

海老原 敬, 菊田 英明

小児科 ( 金原出版(株) )  44 ( 8 ) 1252 - 1257   2003年07月

2001年,オランダのOsterhausらは,急性上気道炎,急性細気管支炎,肺炎などの気道感染症の小児から新しいパラミクソウイルスを分離し,このウイルスをヒト・メタニューモウイルスと命名した.彼らは,5歳迄に大多数がこのウイルスの初感染を受け,RSウイルス(RSV)と同様の症状を呈すると報告した.その後,小児だけでなく成人,免疫不全状態の患者の気道感染症からもこのウイルスが同定されたことから,再感染を起こす可能性が示唆されている.本ウイルスによる感染症は今後,RSVと同様に,特に乳幼児の気道感染症として重要な位置を占めるものと推測される

慢性活動性EBV感染症におけるEBV latency及びEBNA promoterの解析

吉岡 幹朗, 石黒 信久, 馬 暁明, 海老原 敬, 遠藤 理香, 菊田 英明, 小林 邦彦

小児感染免疫 ( (一社)日本小児感染症学会 )  15 ( 2 ) 272 - 272   2003年07月

新しく発見されたhuman metapneumovirusに対する抗体の測定

海老原 敬, 遠藤 理香, 馬 暁明, 吉岡 幹郎, 石黒 信久, 菊田 英明, 小林 邦彦

小児感染免疫 ( (一社)日本小児感染症学会 )  15 ( 2 ) 270 - 270   2003年07月

新しく発見されたhuman metapneumovirusに対する抗体の測定

海老原 敬, 遠藤 理香, 馬 暁明, 吉岡 幹朗, 石黒 信久, 菊田 英明

日本小児科学会雑誌 ( (公社)日本小児科学会 )  107 ( 5 ) 848 - 848   2003年05月

小児の咽頭炎患者から分離されたA群レンサ球菌(GAS)の血清型(M型,T型),遺伝子型(emm型)の検討,およびprtF1遺伝子,sic遺伝子の検出

馬 暁明, 吉岡 幹朗, 石黒 信久, 海老原 敬, 菊田 英明, 小林 邦彦

小児感染免疫 ( 日本小児感染症学会 )  15 ( 1 ) 130 - 130   2003年04月

Comparison of the seroprevalence of human metapneumovirus and human respiratory syncytial virus

Takashi Ebihara, Rika Endo, Hideaki Kikuta, Nobuhisa Ishiguro, Hiroaki Ishiko, Kunihiko Kobayashi

Journal of Medical Virology ( Wiley )  72 ( 2 ) 304 - 306   2003年

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Association of the prtF1 gene (encoding fibronectin-binding protein F1) and the sic gene (encoding the streptococcal inhibitor of complement) with emm types of group A streptococci isolated from Japanese children with pharyngitis

Ma, X., Kikuta, H., Ishiguro, N., Yoshioka, M., Ebihara, T., Murai, T., Kobayashi, I., Kobayashi, K.

Journal of Clinical Microbiology   40 ( 10 )   2002年

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