2003 Fiscal Year Annual Research Report

感染症と免疫病の分子生物学と医学

Research Project

Project/Area Number	09CE2007
Research Institution	Osaka University
Principal Investigator	山西弘一大阪大学, 医学系研究科, 教授 (10029811)
Co-Investigator(Kenkyū-buntansha)	審良静男大阪大学, 微生物病研究所, 教授 (50192919) 菊谷仁大阪大学, 微生物病研究所, 教授 (80161412) 木下タロウ大阪大学, 微生物病研究所, 教授 (10153165)
Keywords	GPIアンカー / PIG-V / Sema4A / sema6D / TLR / MyD88非依存症性経路 / gH-gL-gO / LANA
Research Abstract	(木下)1.ヒトのGPIアンカー生合成遺伝子群の解明に関し、PIG-Vが第2のマンノース転移酵素であること、PIG-Wがイノシトールへのアシル転移酵素であること、PGAP1がイノシトール・デアシラーゼであることを証明した。これにより、GPIアンカーが小胞体膜の細胞質側から内腔側へフリップするステップを除き、生合成の全ステップに働く遺伝子群が解明された。2.睡眠病トリパノソーマのGPIアンカー生合成遺伝子群の解明に関し、アンカーをタンパク質に付加するGPIトランスアミダーゼにヒトには存在しない2つのタンパク質(TTA1,TTA2)が必須であることを見いだした。これらのタンパク質は、睡眠病治療薬の標的に適している。 (菊谷)これまでクラスIVセマフォリンSema4AがTIM2を介してT細胞を刺激することを報告してきたが、本年度はSema4A欠損マウスを作成し、その解析からSema4Aが抗原特異的T細胞の分化、特にTh1細胞に必須であることを示した。また、新規クラスVIセマファリンSema6Dをクローニングし、Sema6Dがその受容体Plexin-A1を介して心内皮細胞の遊走を調節し、心臓形態形成に必須の役割を果たすことを明らかにした。さらに、Sema6Dは免疫系においても樹状細胞のサイトカイン産生を誘導するなどの生物活性を有することが明らかになった。 (審良)Toll Like Receptor(TLR)を介した細胞内シグナル伝達では、全てのTLRの炎症性サイトカインの誘導に必須のMyD88依存性経路と、TLR3,4を介しInterfron(IFN)-β,IFN誘導性遺伝子を誘導するMyD88非依存性経路が存在する。MyD88と同じTIRドメインを持つアダプター群のノックアウトマウスの作製、解析を行った。TIRAPはTLR2,4を介したMyD88依存性経路に関与していた。データベースから同定したTRIFはTLR3,4を介するMyD88非依存性経路に、TRAMはTLR4を介するMyD88依存性経路にだけかかわるアダプターであることを明らかにした。TLRを介したシグナルはアダプター群が制御しその特異性も規定していることがわかった。 (山西)1.ヒトヘルペスウイルス7(HHV7)U12遺伝子が機能的なβケモカインレセプターであることを明らかにした。これによりU12遺伝子産物が何らかのかたちで病態発症にかかわっていることが示唆された。ヒトヘルペスウイルス6(HHV6)variant AのgH-gL-gQがCD46と相互作用すること、HHV6 A U100遺伝子産物がgH-gLコンプレックスの形成因子の一つになっていることなどが明らかになった。Variant Aとvariant Bではウイルス粒子膜分子の形成が異なっており、これが感染細胞の特異性を決めているものと思われる。2.カポジ肉腫関連ヘルペスウイルス(KSHV)では、前初期遺伝子RTAがアポトーシスインデューサーであるにも関わらず、感染細胞ではXIAPの発現上昇によりこの機能が阻止されることを明らかにした。この機構にはORF57遺伝子産物と宿主細胞因子PCBP1が相互作用することにより、XIAP遺伝子のIRESの機能を上昇させることが主な理由であることを突き止めた。潜伏感染状態はウイルス遺伝子latency associated nuclear antigen(LANA)がヒストンメチラーゼSUV39H1と相互作用し、ゲノムをヘテロクロマチン化することにより誘導され、このことが潜伏感染での遺伝子発現プロファイルに強く関わっていることを明らかにした。

Research Products

(99 results)

All Other

All Publications (99 results)

[Publications] Toyofuku, T., et al.: "Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with Off-Track and vascular endothelial growth factor receptor type 2."Genes.Develp. (In press). (2004)
[Publications] Tanaka, S., et al.: "Inositol-deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p."J.Biol.Chem. (In press). (2004)
[Publications] Nishimura, J., et al.: "Clinical course and flow cytometric analysis of PNH in the USA and Japan."Medicin. (In press). (2004)
[Publications] Campos, M.A., et al.: "Impaired production of proinflammatory cytokines and host resistance to acute infection with trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88."J.Immunol.. 172. 1711-1718 (2004)
[Publications] Inoue, H., et al.: "Role of STAT3 in regulation of hepatic gluconegenic genes and carbohydrate metabolism in vivo."Nat.Med.. (In press). (2004)
[Publications] Sasaki, H., et al.: "Gamma interferom (IFN-g) and IFN-g-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resoption in vivo."Clin.Diagn.Lab.Immunol.. 11. 106-110 (2004)
[Publications] Into, T., et al.: "Stimulation of human Toll-like receptor (TLR)2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apopototic cell death after NF-kB activation."Cell Microbiol.. 6. 187-199 (2004)
[Publications] Hokuto, I., et al.: "Stat-3 is required for pulmonary homeostasis during hyperxja."J.Clin.Invest.. 113. 28-37 (2004)
[Publications] Yamamoto, M., et al.: "TIR domain-containing adaptors define the specificity of TLR signalin."Mol.Immunol.. 40. 861-868 (2004)
[Publications] Wan, J., et al.: "Z. Elucidation of the c-Jun N-terminal kinase pathway mediated by Estein-Barr virus-encoded latent membrane protein 1."Mol.Cell.Biol.. 24. 192-199 (2004)
[Publications] Serbina, N.V., et al.: "E.G. Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection."Immunity.. 19. 891-901 (2004)
[Publications] Fujimoto, M., et al.: "Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases."Int Immunol.. 16(2). 303-314 (2004)
[Publications] Ito, H., et al.: "A Pilot Randomized Trial of a Human Anti-Interleukin-6 Receptor Monoclonal Antibody in Active Crohn's Disease."Gastroenterol.. (In press). (2004)
[Publications] Sugawara, I., et al.: "Mycobacterial Infection in MyD88-Deficient Mice."Microbiol Immunol.. 47. 841-847 (2003)
[Publications] Misra, A., et al.: "Functional significance of toll-like receptor-2 mediated signaling in the heart following acute ischemia/infarction."J Am Coll Cardiol.. 41(6 Suppl B). 372 (2003)
[Publications] Iiyama, R., et al.: "Normal Development of the Gut-Associated Lymphoid Tissue Except Peyer's Patch in MyD88-Deficient Mice."Scand J Immunol. 58. 620-627 (2003)
[Publications] Matsukawa, A., et al.: "Aberrant Inflammation and Lethality to Septic Peritonitis in Mice Lacking STAT3 in Macrophages and Neutrophils."J Immunol.. 171. 6198-6205 (2003)
[Publications] Joosten, L.A., et al.: "W.B. Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation : critical role of myeloid differentiation actor 88."J Immunol.. 171. 6145-6153 (2003)
[Publications] Suzuki, N., et al.: "IL-1R-Associated Kinase 4 Is Required for Lipopolysaccharide-Induced Activation of APC."J Immunol.. 171. 6065-6071 (2003)
[Publications] Akira, S., et al.: "Toll-like receptors and their signaling mechanisms."Scand J Infect Dis.. 33. 555-562 (2003)
[Publications] Schirmbeck, R., et al.: "Antigenic Epitopes Fused to gationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4(+) T Cell Help-Independent, Priming of CD8(+)T Cells."J Immunol.. 171. 5198-5207 (2003)
[Publications] Heil, F., et al.: "The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7,8 and 9 subfamily."Eur J Immunol.. 33. 2987-2997 (2003)
[Publications] Yamamoto, M., et al.: "TRAM is specifically involved in thte Toll-like receptor 4-mediated MyD88-independent signaling pathway."Nat.Immunol.. 1144-1150 (2003)
[Publications] Krug, A., et al.: "Herpes simplex virus type 1 (HSV-1) activates murine Natural Interferon-Producing cells (IPC) through Toll-Like Receptor 9."Blood.. (In press). (2003)
[Publications] Takahashi, K., et al.: "X-ray crystal structure of IRF-3 and its functional Implications."Nat Struct Biol.. 10. 922-927 (2003)
[Publications] Sato, S., et al.: "Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-Binding kinase 1, and activates two distinct transcription factors, NF-kappaB and IFN-regulatory factor-3, in the Toll-like receptor signaling."J Immunol.. 171. 4304-4310 (2003)
[Publications] Haga, S., et al.: "Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms."J.Clin Invest.. 112. 989-998 (2003)
[Publications] Shi, S., et al.: "MyD88 Primes Macrophages for Full-Scale Activation by Interferon-γ yetMediates Few Responses to Mycobacterium tuberculosis."J Exp Med.. 198. 987-998 (2003)
[Publications] Weijer, S., et al.: "Interleukin-18 Facilitates the Early Antimicrobial Host Response to Escherichia coli Peritonitis."Infect Immun. 71. 5488-5497 (2003)
[Publications] Cheng, F., et al.: "A critical role for stat3 signaling in immune tolerance."Immunity.. 19. 425-436 (2003)
[Publications] Kariyone, A., et al.: "Immunogenicity of Peptide-25 of Ag85 in Th1 development : role of IFN-g."Int.Immunol.. 15. 1183-1194 (2003)
[Publications] Heli, F., et al.: "The Toll-like receptor 7(TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7,8,and 9 sub family."Eur.J.Immmunol.. 2987-2997 (2003)
[Publications] Honda, K., et al.: "Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection."Proc Natl Acad Sci USA.. 10872-10877 (2003)
[Publications] Zhang, J.H., et al.: "Analysis of crytokine regulators inducing interferon production by mmouse uterine natural killer cells."Biol.Of Reproduction.. 69. 404-411 (2003)
[Publications] Goldstein, D.R., et al.: "Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection."J.Clin.Invest.. 111. 1571-1578 (2003)
[Publications] Kaisho, T., et al.: "Regulation of dendritic cell function through Toll-like receptors."Curr.Mol.Med.. 3. 373-385 (2003)
[Publications] Akira, S., et al.: "Myeloid differentiation factor 88-dependent and -independent pathways in toll-like receptor signaling."J.Infect.Dis. 15:Suppl2. S356-S363 (2003)
[Publications] Kojima, E., et al.: "The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress : elucidation by GADD34-deficient mice."FASEB J.. 17. 1573-1575 (2003)
[Publications] Jouault, T., et al.: "Candida albicans phospholipomannan is sensed through toll-like receptors."J.Infect.Dis.. 188. 165-172 (2003)
[Publications] Mun, H.S., et al.: "TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection."Int, Immunol.. 15. 1081-1087 (2003)
[Publications] Sugawara, I., et al.: "Mycobacterial infection in TLR2 and TLR6 knockout mice."Microbial.Immunol.. 47. 327-336 (2003)
[Publications] Elhage, R., et al.: "Reduced atherosclerosis in interleukin-18 defcient apolipoprotein E-knockout mice. Cardiovasc."Cardiovasc.Res. 59. 234-240 (2003)
[Publications] Tamai, R., et al.: "Synergistic effects of lipopolysaccharide and interferon-gamma in inducing interleukin-8 production in human monoeytic THP-1 cells is accompanied by up-regulation of CD14,Toll-like receptor 4,MD-2 and MyD88 expression."J.Endotoxin Res. 9. 145-153 (2003)
[Publications] Kawai, T., et al.: "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains."Mol.Cell.Biol.. 23. 6174-6186 (2003)
[Publications] Lund, J., et al.: "Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells."J.Exp.Med.. 198. 513-520 (2003)
[Publications] Ebisuno, Y., et al.: "Cutting edge : The B cell chemokine CXC chemokine ligand 13/B lymphocyte chemoattractant is expressed in the high endothelial venules If lymph nodes and Payer's patches and affects B cell trafficking across high endothelial venuls."J.Immunol.. 15. 1642-1646 (2003)
[Publications] Kuwata, H., et al.: "IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-α production in macrophages."Blood. 102. 4123-4129 (2003)
[Publications] Marr, K.A., et al.: "Conrad Liles, W.Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens."Infect.Immunol.. 71. 5280-5286 (2003)
[Publications] Takagi, H., et al.: "Contrasting action of IL-12 and II-18 in the development of dextran sodium sulphate colitis in mice."Scand J.Gastroenterol. 838. 837-844 (2003)
[Publications] Shibue, T., et al.: "Integral role of Noxa in p53-mediated apoptotic response."Genes Dev.. 17. 2233-2248 (2003)
[Publications] Tsutui, H., et al.: "IL-18 and IL-18 receptor knockout mice."Contemporary Immunol : Cytokine knockouts, 2^<nd> Edition. 303-322 (2003)
[Publications] Uehori, J., et al.: "Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Macobacterium bovis bacillus calmette-guerin peptidoglycan."Infect.Immunol.. 4238-4249 (2003)
[Publications] Yamamoto, M., et al.: "Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway."Science. 640-643 (2003)
[Publications] Maruoka O., et al.: "Leptin-induced transactivation of NPY gene promotoer mediated by JAK1,JAK2 and STAT3 in the neural cell lines."Neurochem Int.. 42. 591-601 (2003)
[Publications] Yasukawa, H., et al.: "IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages."Nature Immunol.. 4. 551-556 (2003)
[Publications] Liu, N., et al.: "CpG directly induces T-bet expression and inhibits Igγ1 and Igε switching in B cells."Nature Immunol.. 4. 687-693 (2003)
[Publications] Akira.S., et al.: "Role of adapters in Toll-like receptor signaling."Biochem.Soc.Trans.. 31. 637-642 (2003)
[Publications] Kaisho, T., et al.: "Regulation of dendritic cell function through Toll-like receptors."Curr.Mol.Med. 3. 373-385 (2003)
[Publications] Yokozeki, H., et al.: "Th2 cytokines, IgE and mast cells play a crucial role in the induction of para-phenylenediamine-induced contact hypersensitivity in mice."Clin.Exp.Immunol.. 132. 385-392 (2003)
[Publications] Akira, S., et al.: "Myelold differentiation factor 88-dependent and -independent pathways in toll-like receptor signaling."J.Infect.Dis.. 187:Suppl2. S356-S363 (2003)
[Publications] Okamoto, M., et al.: "Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432."J.Natl.Cancer Inst.. 95. 316-326 (2003)
[Publications] Prinz, M., et al.: "Prion pathogenesis in the absence of Toll-like receptor signaling."EMBO Rep.. 4. 195-199 (2003)
[Publications] Takeda, K., et al.: "Toll receptors and pathogen resistance."Cell Microbiol.. 5. 143-153 (2003)
[Publications] Hazeki, K., et al.: "Toll-like receptor-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and-independent pathways."J.Immunol.. 33. 740-747 (2003)
[Publications] Hemmi, H., et al.: "The roles of Toll-like receptor 9,MyD88,and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets."J.Immunol.. 170. 3059-3064 (2003)
[Publications] Akira, S., et al.: "Mammalian Toll-like receptors."Curr.Opin.Immunol.. 15. 238 (2003)
[Publications] Schultz, M., et al.: "Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa."Infect.Immun.. 71. 1630-1634 (2003)
[Publications] Edwards A., et al.: "Toll-like receptor expression in murine DC subsets : lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines."Eur J.Immunol.. 33. 827-833 (2003)
[Publications] Kruzik, S.R., et al.: "Activation and regulation of Toll-like receptors 2 and 1 in human leprosy."Nature.. 9. 525-532 (2003)
[Publications] Takeda, K., et al.: "Recognition of lipopeptides by Toll-like receptors.J.Endotoxin Res."J.Endotoxin Res. 8. 459-463 (2003)
[Publications] Datta, S., et al.: "A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells."J.Immunol.. 170. 4102-4110 (2003)
[Publications] Yazawa, N., et al.: "CD19 regulates innate immunity by the toll-like receptor RP105 signaling in B lymphocytes."Blood.. (In press). (2003)
[Publications] Ganter, B.N., et al.: "Collaborative induction of inflammatory resposes by Dection-1 and toll-like receptor 2."J.Exp.Med.. 197. 1107-1117 (2003)
[Publications] Kobayashi, M., et al.: "Toll-like receptor-dependent production of IL-12p40 causes choronic enterocolitis in myeloid cell-specific Stat3-deficient mice."J.Clin.Invest.. 111. 1297-1308 (2003)
[Publications] Zwijnenburg, P.J., et al.: "Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis."J.Nueroimmunol.. 138. 31-37 (2003)
[Publications] Goldstein, D.R., et al.: "Crinical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograht rejection."J.Clin.Invest.. 111. 1571-1578 (2003)
[Publications] Yasukawa, H., et al.: "IL-6 induces an anti-infllamatory response in the absence of SOCS3 in macrophages."Nat.Immunol.. 4. 551-556 (2003)
[Publications] Hong, Y., et al.: "Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins."Mol.Biol.Cell. 14. 1780-1789 (2003)
[Publications] Ohishi, K., et al.: "Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins."J.Biol.Chem.. 278. 13959-13967 (2003)
[Publications] Murakami, Y., et al.: "PIG-W is critical for inositol acylation but not for flipping of glycosylphosphatidylinositol-anchor."Mol.Biol.Cell. 14. 4285-4295 (2003)
[Publications] Nagamune, K., et al.: "GPI transamidase of Trypanosoma brucei has two novel (TTA1 and TTA2) and three common subunits."Proc.Natl.Acad.Sci.USA. 100. 10682-10687 (2003)
[Publications] Inoue, N., et al.: "Molecular genetics of paroxysmal nocturnal hemoglobinuria."Int.J.Hematol.. 77. 107-112 (2003)
[Publications] Kumanogoh, A., et al.: "Roles of the semaphorin family in immune regulation."Adv.Immunol.. 81. 173-198 (2003)
[Publications] Stratmann, T., et al.: "Susceptible MHC alleles, not background genes, select and autoimmune T cell reactivity."J.Glin.Invest.. 112. 902-914 (2003)
[Publications] Moreau-Fauvarque., et al.: "The transmembrane semaphorin Sema4D/CD100,and inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion."J.Neurosci.. 23. 9229-9239 (2003)
[Publications] Kumanogoh., et al.: "Immune semaphorins : a New area of semaphore research."J.Cell.Sci.. 116. 3463-3479 (2003)
[Publications] Ishida, I., et al.: "Involvement of CD100,a lymphocyte semaphorin, in the activation of the human immune system via CD72 : implications for the regulation of immune and inflammatory responses."Int.Immunol.. 15. 1027-1034 (2003)
[Publications] Takahashi, H., et al.: "Increased susceptibility to airway responses in CD40-deficient mice."Clin.Exp.Immunol.. 133. 22-29 (2003)
[Publications] Kikutani, H, et al.: "Semaphorins in interactions between T cells and antigen-presenting cells."Nat Rev Immunol.. 31. 159-167 (2003)
[Publications] Suzuki, K., et al.: "CD100/Sema4D, a lymphocyte semaphorin involved in the regulation of humoral and cellular immune responses."Cytokine Growth Factor Rev.. 14. 17-24 (2003)
[Publications] Mori, Y., et al.: "The Human Herpesvirus 6 U100 Gene Product Is the Third Component of the gH-gL Glycoprotein Complex on the Viral Envelope."J Virol.. 77. 2452-2458 (2003)
[Publications] Amo, K., et al.: "Human herpesvirus 6B infection of the large intestine of patients with diarrhea."Clin Infect Dis. 36. 120-123 (2003)
[Publications] Mori, Y., et al.: "Human Herpesvirus 6 Variant A Glycoprotein H-Glycoprotein L-Glycoprotein.Q Complex Associates with Human CD46."J Virol.. 77. 4992-4999 (2003)
[Publications] Kondo, K., et al.: "Recognition of a novel stage of betaherpesvirus latency in human herpesvirus 6."J Virol.. 77. 2258-2264 (2003)
[Publications] Nakano, K., et al.: "Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells."Arch Virol.. 148. 871-890 (2003)
[Publications] Kondo, K., et al.: "Detection of a gene cluster that is dispensable for human herpesvirus 6 replication and latency."J Virol.. 77. 10719-10724 (2003)
[Publications] Nakano, K., et al.: "Human herpesvirus 7 open reading frame U12 encodes a functional beta-chemokine receptor."J Virol.. 77. 8108-8115 (2003)
[Publications] Nishimura, K., et al.: "A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus (KSHV) induces apoptosis, which is blocked in KSHV-infected cells."Virology. 316. 64-74 (2003)
[Publications] Lufting, M., et al.: "Epstein-Barr virus latent membrane protein1 activation of NF-kB through IRAK1 and TRAF6."Proc.Natl.Acad.Scit.USA. 15595-15600 (2003)

2003 Fiscal Year Annual Research Report

感染症と免疫病の分子生物学と医学

Principal Investigator

山西 弘一 大阪大学, 医学系研究科, 教授 (10029811)

Research Products

[Publications] Toyofuku, T., et al.: "Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with Off-Track and vascular endothelial growth factor receptor type 2."Genes.Develp. (In press). (2004)

[Publications] Tanaka, S., et al.: "Inositol-deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p."J.Biol.Chem. (In press). (2004)

[Publications] Nishimura, J., et al.: "Clinical course and flow cytometric analysis of PNH in the USA and Japan."Medicin. (In press). (2004)

[Publications] Campos, M.A., et al.: "Impaired production of proinflammatory cytokines and host resistance to acute infection with trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88."J.Immunol.. 172. 1711-1718 (2004)

[Publications] Inoue, H., et al.: "Role of STAT3 in regulation of hepatic gluconegenic genes and carbohydrate metabolism in vivo."Nat.Med.. (In press). (2004)

[Publications] Sasaki, H., et al.: "Gamma interferom (IFN-g) and IFN-g-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resoption in vivo."Clin.Diagn.Lab.Immunol.. 11. 106-110 (2004)

[Publications] Into, T., et al.: "Stimulation of human Toll-like receptor (TLR)2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apopototic cell death after NF-kB activation."Cell Microbiol.. 6. 187-199 (2004)

[Publications] Hokuto, I., et al.: "Stat-3 is required for pulmonary homeostasis during hyperxja."J.Clin.Invest.. 113. 28-37 (2004)

[Publications] Yamamoto, M., et al.: "TIR domain-containing adaptors define the specificity of TLR signalin."Mol.Immunol.. 40. 861-868 (2004)

[Publications] Wan, J., et al.: "Z. Elucidation of the c-Jun N-terminal kinase pathway mediated by Estein-Barr virus-encoded latent membrane protein 1."Mol.Cell.Biol.. 24. 192-199 (2004)

[Publications] Serbina, N.V., et al.: "E.G. Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection."Immunity.. 19. 891-901 (2004)

[Publications] Fujimoto, M., et al.: "Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases."Int Immunol.. 16(2). 303-314 (2004)

[Publications] Ito, H., et al.: "A Pilot Randomized Trial of a Human Anti-Interleukin-6 Receptor Monoclonal Antibody in Active Crohn's Disease."Gastroenterol.. (In press). (2004)

[Publications] Sugawara, I., et al.: "Mycobacterial Infection in MyD88-Deficient Mice."Microbiol Immunol.. 47. 841-847 (2003)

[Publications] Misra, A., et al.: "Functional significance of toll-like receptor-2 mediated signaling in the heart following acute ischemia/infarction."J Am Coll Cardiol.. 41(6 Suppl B). 372 (2003)

[Publications] Iiyama, R., et al.: "Normal Development of the Gut-Associated Lymphoid Tissue Except Peyer's Patch in MyD88-Deficient Mice."Scand J Immunol. 58. 620-627 (2003)

[Publications] Matsukawa, A., et al.: "Aberrant Inflammation and Lethality to Septic Peritonitis in Mice Lacking STAT3 in Macrophages and Neutrophils."J Immunol.. 171. 6198-6205 (2003)

[Publications] Joosten, L.A., et al.: "W.B. Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation : critical role of myeloid differentiation actor 88."J Immunol.. 171. 6145-6153 (2003)

[Publications] Suzuki, N., et al.: "IL-1R-Associated Kinase 4 Is Required for Lipopolysaccharide-Induced Activation of APC."J Immunol.. 171. 6065-6071 (2003)

[Publications] Akira, S., et al.: "Toll-like receptors and their signaling mechanisms."Scand J Infect Dis.. 33. 555-562 (2003)

[Publications] Schirmbeck, R., et al.: "Antigenic Epitopes Fused to gationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4(+) T Cell Help-Independent, Priming of CD8(+)T Cells."J Immunol.. 171. 5198-5207 (2003)

[Publications] Heil, F., et al.: "The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7,8 and 9 subfamily."Eur J Immunol.. 33. 2987-2997 (2003)

[Publications] Yamamoto, M., et al.: "TRAM is specifically involved in thte Toll-like receptor 4-mediated MyD88-independent signaling pathway."Nat.Immunol.. 1144-1150 (2003)

[Publications] Krug, A., et al.: "Herpes simplex virus type 1 (HSV-1) activates murine Natural Interferon-Producing cells (IPC) through Toll-Like Receptor 9."Blood.. (In press). (2003)

[Publications] Takahashi, K., et al.: "X-ray crystal structure of IRF-3 and its functional Implications."Nat Struct Biol.. 10. 922-927 (2003)

[Publications] Haga, S., et al.: "Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms."J.Clin Invest.. 112. 989-998 (2003)

[Publications] Shi, S., et al.: "MyD88 Primes Macrophages for Full-Scale Activation by Interferon-γ yetMediates Few Responses to Mycobacterium tuberculosis."J Exp Med.. 198. 987-998 (2003)

[Publications] Weijer, S., et al.: "Interleukin-18 Facilitates the Early Antimicrobial Host Response to Escherichia coli Peritonitis."Infect Immun. 71. 5488-5497 (2003)

[Publications] Cheng, F., et al.: "A critical role for stat3 signaling in immune tolerance."Immunity.. 19. 425-436 (2003)

[Publications] Kariyone, A., et al.: "Immunogenicity of Peptide-25 of Ag85 in Th1 development : role of IFN-g."Int.Immunol.. 15. 1183-1194 (2003)

[Publications] Heli, F., et al.: "The Toll-like receptor 7(TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7,8,and 9 sub family."Eur.J.Immmunol.. 2987-2997 (2003)

[Publications] Honda, K., et al.: "Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection."Proc Natl Acad Sci USA.. 10872-10877 (2003)

[Publications] Zhang, J.H., et al.: "Analysis of crytokine regulators inducing interferon production by mmouse uterine natural killer cells."Biol.Of Reproduction.. 69. 404-411 (2003)

[Publications] Goldstein, D.R., et al.: "Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection."J.Clin.Invest.. 111. 1571-1578 (2003)

[Publications] Kaisho, T., et al.: "Regulation of dendritic cell function through Toll-like receptors."Curr.Mol.Med.. 3. 373-385 (2003)

[Publications] Akira, S., et al.: "Myeloid differentiation factor 88-dependent and -independent pathways in toll-like receptor signaling."J.Infect.Dis. 15:Suppl2. S356-S363 (2003)

[Publications] Kojima, E., et al.: "The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress : elucidation by GADD34-deficient mice."FASEB J.. 17. 1573-1575 (2003)

[Publications] Jouault, T., et al.: "Candida albicans phospholipomannan is sensed through toll-like receptors."J.Infect.Dis.. 188. 165-172 (2003)

[Publications] Mun, H.S., et al.: "TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection."Int, Immunol.. 15. 1081-1087 (2003)

[Publications] Sugawara, I., et al.: "Mycobacterial infection in TLR2 and TLR6 knockout mice."Microbial.Immunol.. 47. 327-336 (2003)

[Publications] Elhage, R., et al.: "Reduced atherosclerosis in interleukin-18 defcient apolipoprotein E-knockout mice. Cardiovasc."Cardiovasc.Res. 59. 234-240 (2003)

[Publications] Tamai, R., et al.: "Synergistic effects of lipopolysaccharide and interferon-gamma in inducing interleukin-8 production in human monoeytic THP-1 cells is accompanied by up-regulation of CD14,Toll-like receptor 4,MD-2 and MyD88 expression."J.Endotoxin Res. 9. 145-153 (2003)

[Publications] Kawai, T., et al.: "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains."Mol.Cell.Biol.. 23. 6174-6186 (2003)

[Publications] Lund, J., et al.: "Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells."J.Exp.Med.. 198. 513-520 (2003)

[Publications] Kuwata, H., et al.: "IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-α production in macrophages."Blood. 102. 4123-4129 (2003)

[Publications] Marr, K.A., et al.: "Conrad Liles, W.Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens."Infect.Immunol.. 71. 5280-5286 (2003)

[Publications] Takagi, H., et al.: "Contrasting action of IL-12 and II-18 in the development of dextran sodium sulphate colitis in mice."Scand J.Gastroenterol. 838. 837-844 (2003)

[Publications] Shibue, T., et al.: "Integral role of Noxa in p53-mediated apoptotic response."Genes Dev.. 17. 2233-2248 (2003)

[Publications] Tsutui, H., et al.: "IL-18 and IL-18 receptor knockout mice."Contemporary Immunol : Cytokine knockouts, 2^<nd> Edition. 303-322 (2003)

[Publications] Uehori, J., et al.: "Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Macobacterium bovis bacillus calmette-guerin peptidoglycan."Infect.Immunol.. 4238-4249 (2003)

[Publications] Yamamoto, M., et al.: "Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway."Science. 640-643 (2003)

[Publications] Maruoka O., et al.: "Leptin-induced transactivation of NPY gene promotoer mediated by JAK1,JAK2 and STAT3 in the neural cell lines."Neurochem Int.. 42. 591-601 (2003)

[Publications] Yasukawa, H., et al.: "IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages."Nature Immunol.. 4. 551-556 (2003)

[Publications] Liu, N., et al.: "CpG directly induces T-bet expression and inhibits Igγ1 and Igε switching in B cells."Nature Immunol.. 4. 687-693 (2003)

[Publications] Akira.S., et al.: "Role of adapters in Toll-like receptor signaling."Biochem.Soc.Trans.. 31. 637-642 (2003)

[Publications] Kaisho, T., et al.: "Regulation of dendritic cell function through Toll-like receptors."Curr.Mol.Med. 3. 373-385 (2003)

[Publications] Yokozeki, H., et al.: "Th2 cytokines, IgE and mast cells play a crucial role in the induction of para-phenylenediamine-induced contact hypersensitivity in mice."Clin.Exp.Immunol.. 132. 385-392 (2003)

[Publications] Akira, S., et al.: "Myelold differentiation factor 88-dependent and -independent pathways in toll-like receptor signaling."J.Infect.Dis.. 187:Suppl2. S356-S363 (2003)

[Publications] Okamoto, M., et al.: "Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432."J.Natl.Cancer Inst.. 95. 316-326 (2003)

[Publications] Prinz, M., et al.: "Prion pathogenesis in the absence of Toll-like receptor signaling."EMBO Rep.. 4. 195-199 (2003)

[Publications] Takeda, K., et al.: "Toll receptors and pathogen resistance."Cell Microbiol.. 5. 143-153 (2003)

[Publications] Hazeki, K., et al.: "Toll-like receptor-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and-independent pathways."J.Immunol.. 33. 740-747 (2003)

[Publications] Hemmi, H., et al.: "The roles of Toll-like receptor 9,MyD88,and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets."J.Immunol.. 170. 3059-3064 (2003)

[Publications] Akira, S., et al.: "Mammalian Toll-like receptors."Curr.Opin.Immunol.. 15. 238 (2003)

[Publications] Schultz, M., et al.: "Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa."Infect.Immun.. 71. 1630-1634 (2003)

[Publications] Edwards A., et al.: "Toll-like receptor expression in murine DC subsets : lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines."Eur J.Immunol.. 33. 827-833 (2003)

[Publications] Kruzik, S.R., et al.: "Activation and regulation of Toll-like receptors 2 and 1 in human leprosy."Nature.. 9. 525-532 (2003)

[Publications] Takeda, K., et al.: "Recognition of lipopeptides by Toll-like receptors.J.Endotoxin Res."J.Endotoxin Res. 8. 459-463 (2003)

[Publications] Datta, S., et al.: "A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells."J.Immunol.. 170. 4102-4110 (2003)

[Publications] Yazawa, N., et al.: "CD19 regulates innate immunity by the toll-like receptor RP105 signaling in B lymphocytes."Blood.. (In press). (2003)

[Publications] Ganter, B.N., et al.: "Collaborative induction of inflammatory resposes by Dection-1 and toll-like receptor 2."J.Exp.Med.. 197. 1107-1117 (2003)

[Publications] Kobayashi, M., et al.: "Toll-like receptor-dependent production of IL-12p40 causes choronic enterocolitis in myeloid cell-specific Stat3-deficient mice."J.Clin.Invest.. 111. 1297-1308 (2003)

[Publications] Zwijnenburg, P.J., et al.: "Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis."J.Nueroimmunol.. 138. 31-37 (2003)

[Publications] Goldstein, D.R., et al.: "Crinical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograht rejection."J.Clin.Invest.. 111. 1571-1578 (2003)

[Publications] Yasukawa, H., et al.: "IL-6 induces an anti-infllamatory response in the absence of SOCS3 in macrophages."Nat.Immunol.. 4. 551-556 (2003)

山西弘一大阪大学, 医学系研究科, 教授 (10029811)