Host Defence

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Our laboratory studies the fundamental mechanisms of innate immunity. The innate immune system senses invading microbial pathogens and plays an essential role for induction of inflammatory responses as well as assisting adaptive immune responses. Germline-encoded pattern-recognition receptors (PRRs) expressed on innate immune cells such as macrophages and dendritic cells are responsible for recognition of pathogen-associated molecular patterns (PAMPs) that represent conserved molecular features in microbial pathogens. Through the generation of knockout mice, we have demonstrated that a family of Toll-like receptors (TLR) recognizes a variety of PAMPs such as lipopolysaccharide (LPS), lipoprotein and nucleic acids derived from bacteria, viruses and protozoa to elicit innate immune responses. We have also demonstrated that a family of RIG-I-like RNA helicases (RLR) including RIG-I, MDA5 and LGP2 participates in TLR-independent recognition of nucleic acids derived from different types of RNA viruses in the cytoplasm. Moreover, we have found that there is an unknown sensor that recognizes double-stranded DNA in the cytoplasm. Based on these findings, our research group is currently investigating following issues.

Maeda group

We are studying molecular mechanisms of innate immune responses associated with RNA metabolism by generating conditional knockout mice models. We also try to understand cellular innate immune responses comprehensively by using the next generation sequencing and by using the super-resolution microscopy. Innate immunity is pivotal not only for host defense to pathogens, but also for development of complex immune diseases such as autoimmune diseases. We are hoping to clarify the contribution of innate immunity in the pathogenesis of immune diseases.

Satoh group
We have identified the new M2 macrophage subsets. There are different types of immune cells, however, our understanding of them is still limited. We have tried to identify the new M2 macrophage subsets, which is responsible for prevent the lung fibrosis. This study would uncover the new phenotype in the immunity how immune system is controlled in our body and develop of potential therapies targets for diseases. We expect that these studies based on our past research guide us in paving the way for our future direction.

Principal Investigator

Shizuo Akira Professor

Research field:Pathogen recognition and innate immunity
+81-6-6879-8302
sakira atmark biken.osaka-u.ac.jp
Education history
1977 Osaka University School of Medicine
1984 Osaka University, Graduate School of Medicine
Research and career history

1977-1980 Clinical Training and Physician
1985-1987 Research Fellow, University of California, Berkeley
1987-1995 Research Associate, Institute for Molecular and Cellular Biology, Osaka University
1995 Associate Professor, Institute for Molecular and Cellular Biology, Osaka University
1996-1999 Professor, Hyogo College of Medicine
1999-present Professor, Research Institute for Microbial Diseases, Osaka University
2007-present Center Director, Osaka University Immunology Frontier Research Center

Members

Kazuhiko Maeda Associate Professor
kazmaeda atmark biken.osaka-u.ac.jp
Mikael Martino Guest Associate Professor
mikael.martino atmark monash.edu
Takashi Satoh Assistant Professor
sohsatoh atmark biken.osaka-u.ac.jp
Hiroki Tanaka Assistant Professor
htanaka atmark ifrec.osaka-u.ac.jp
Shailendra Kumar Singh Researcher
singh-sk atmark ifrec.osaka-u.ac.jp
Kanako Kuniyoshi Researcher
konkon atmark biken.osaka-u.ac.jp
 
 

Publications

Kozaki T, Komano J, Kanbayashi D, Takahama M, Misawa T, Satoh T, Takeuchi O, Kawai T, Shimizu S, Matsuura Y, Akira S, Saitoh T. Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response. Proc Natl Acad Sci U S A. 114(10): 2681-2686 (2017)
Satoh T, Nakagawa K, Sugihara F, Kuwahara R, Ashihara M, Yamane F, Minowa Y, Fukushima K, Ebina I, Yoshioka Y, Kumanogoh A, Akira S. Identification of an atypical monocyte and committed progenitor involved in fibrosis. Nature. 541(7635):96-101 (2017)
Satoh T, Akira S. Toll-Like Receptor Signaling and Its Inducible Proteins. Microbiol Spectr. 6, 4 (2016)
Maeda K, Akira S. TLR7 Structure: Cut in Z-Loop. Immunity. 45(4):705-707 (2016)
Martino MM, Maruyama K, Kuhn GA, Satoh T, Takeuchi O, Muller R, Akira S. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration. Nature Communications. 7:11051 (2016)
Kuniyoshi K, Takeuchi O, Pandey S, Satoh T, Iwasaki H, Akira S, Kawai T. Pivotal role of RNA-binding E3 ubiquitin ligase mEX3C in RIG-I-mediated antiviral innate immunity. Proc Natl Acad Sci U S A. 111(15):5646-5651 (2014)
Lee H, Komano J, Saitoh Y, Yamaoka S, Kozaki T, Misawa T, Takahama M, Satoh T, Takeuchi O, Yamamoto N, Matsuura Y, Saitoh T, Akira S. Zinc-finger antiviral protein mediates retinoic acid inducible gene I-like receptor-independent antiviral response to murine leukemia virus. Proc Natl Acad Sci U S A. 110(30):12379-12384 (2013)
Uehata T, Iwasaki H, Vandenbon A, Matsushita K, Hernandez-Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O, Akira S. Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation. Cell. 153(5):1036-1049 (2013)
Zou J, Kawai T, Tsuchida T, Kozaki T, Tanaka H, Shin KS, Kumar H, Akira S. Poly IC Triggers a Cathepsin D- and IPS-1-Dependent Pathway to Enhance Cytokine Production and Mediate Dendritic Cell Necroptosis. Immunity. 38(49):717-728 (2013)
Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S. Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages. Nature. 495(7442):524-528 (2013)
Misawa T, Takahama M, Kozaki T, LeeH, Zou J, Saitoh T, Akira S. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 14(5):454-460 (2013)
Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K, Satoh T, Saitoh T, Matsushita M, Standley DM, Akira S. The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol. 12(12):1167-1175 (2011)
Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S. Antiviral Protein Viperin Promotes Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Type I Interferon Production in Plasmacytoid Dendritic Cells. Immunity. 34(3):352-63 (2011)
Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, Kawai T, Akira S. The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA. Immunity. 33(5):765-776 (2010)
Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 11(10):936-944 (2010)
Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci U S A. 107(4):1512-1517 (2010)
Saitoh T, Fujita N, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T, Yamamoto N, Kawai T, Ishii K, Takeuchi O, Yoshimori T, Akira S. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A. 106(49):20842-20846 (2009)
Kawagoe T, Takeuchi O, Takabatake Y, Kato H, Isaka Y, Tsujimura T, Akira S. TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat Immunol. 10(9):965-972 (2009)
Matsushita K, Takeuchi O, Standley DM, Kumagai Y, Kawagoe T, Miyake T, Satoh T, Kato H, Tsujimura T, Nakamura H, Akira S. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature. 458(7242):1185-1190 (2009)
Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 456(7219):264-268 (2008)

Prize

2012 Frederik B. Bang Award(IEIIS)
2011 Gairdner International Award
2010 Keio Medical Science Prize
2010 Avery-Landsteiner Prize
2009 Person of Cultural Merit
2009 Foreign Associate, National Academy of Science
2007 Milstein Award
2007 The Japan Academy Award The Imperial Award
2007 Uehara Prize
2006 William B Coley Award
2006 Asahi Prize
2005 The Emperor's Purple Ribbon Medal
2004 Robert Koch Prize
2004 Prize of Pricess Takamatsu Cancer Reseach Fund
2003 Takeda Medical Prize
2002 Osaka Science Prize
2001 Hideyo Noguchi Prize
2000 Inoue Prize for Science

Editor/Editorial Board

Special mention

2016 Highly Cited Researchers “Biology & Biochemistry, Immunology” (Thomson Reuters)
2014 Highly Cited Researchers “Biology & Biochemistry”, “Clinical Medicine”, “Immunology” (Thomson Reuters)
2014 Lerner Lecture (Cleveland Clinic Lerner Research Institute, USA)
2014 Distinguished LUDWIG Lecture (Universite de Lausanne, Germany)
2010 17th Dundee Cell Signaling Lecture (University of Dundee, Scotland)
2009 Lacey Lecture (Washington University at St. Louis, Germany)
2008 Dyer Lecture (National Institutes of Health, USA)
2007 Dunham Lectures (Harvard Medical School, USA)
2007 Doctor of Medical Science at Technical University of Munich
2006 and 2007 "Hottest Researcher" in all research fields for two consecutive years (Thomson Scientific Research)
The top cited immunologist since 2004 (Thomson Scientific Research)