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Principle Investigators, Research Themes

Yoichiro Iwakura Elucidation of the pathogenic mechanisms of allergic and autoimmune diseases and development of new therapeutics targeted on IL-17 family molecules and C-type lectin recepors.
Toshiaki Ohteki Conquest of mucosal immune disorders on the basis of dendritic cell regulation
Toshiyuki Takai Novel immunotherapies exploiting inhibitory mechanisms of immunoreceptors
Shigekazu Nagata Engulfment and degradation of apoptotic cells, and its failure
Toshio Hirano Mechanis of organ specific inflammatory/autoimmune diseases and the development of its control approach
Yoshinori Fukui A novel strategy for treatment of immune-related disorders by using cytoskeleton regulating signals as targets
Akihiko Yoshimura Reprograming of immune system by modulation of intracellular signal transduction

Elucidation of the pathogenic mechanisms of allergic and autoimmune diseases and development of new therapeutics targeted on IL-17 family molecules and C-type lectin recepors.

Researcher's name Yoichiro Iwakura
Research Site Professor, Tokyo University of Science
Content Upon infection, immune cells are activated and produce cytokines through recognition of these pathogens by pathogen-associated molecular pattern recognition molecules such as TLR or C-type lectins, resulting in the eladication of these pathogens. However, excess activation of this system may also cause allergy and autoimmunity. In this project, we will analyze the functional roles of cytokines including IL-17A/IL-17F and C-type lectins including Dectin-1/2 and Dcir in the development of diseases such as rheumatoid arthritis, allery, and infectious diseases, and try to develop novel therapeutics against these diseases.

Conquest of mucosal immune disorders on the basis of dendritic cell regulation

Researcher's name Toshiaki Ohteki
Research Site Professor, Tokyo Medical and Dental University
URL http://www.med.akita-u.ac.jp/~kisei/Default.html
Content Mucosa is a major entry site for antigens and its associated lymphoid tissues comprise a unique system of dendritic cells (DC) that maintains immune tolerance. In this research project, we will elucidate the induction mechanisms of DC-mediated mucosal immune tolerance and disorders. Based on the results, we will further aim at the development of DC-based technology for prevention and treatment of mucosal immune disorders.

Main Research Collaborators list

Iwata, Makoto Professor, Tokushima Bunri University
Inaba, Kayo Professor, Kyoto University
Kadowaki, Norimitsu Professor, Kyoto University

Novel immunotherapies exploiting inhibitory mechanisms of immunoreceptors

Researcher's name Toshiyuki Takai
Research Site Professor, Tohoku University
URL http://www.idac.tohoku.ac.jp/dep/expimu/
Content We will establish novel therapeutic strategies against allergic and autoimmune diseases by enhancing immunoregulatory poteintials of cell-surface receptors, such as FcgRIIB and LILRB, critical inhibitory receptors for IgG and MHC class I molecules, respectively. We plan polishing-up of intravenous g-globulin therapies and enhancement of self-tolerance by developing agonistic ligands to the critical immunoregulatory receptors. Moreover, we will examine these basic and pre-clinic ideas in NOG mice with the humanized immune system, and will maturate our original concept into the development of versatile immunoregulatory tools for the immune system in humans.

Engulfment and degradation of apoptotic cells, and its failure

Researcher's name Shigekazu Nagata
Research Site Professor, Kyoto University
URL http://www2.mfour.med.kyoto-u.ac.jp/~nagata/
Content Everyday several billions of cells undergo apoptosis in our bodies. They are swiftly engulfed by macrophages for degradation. More than 10 billions of red blood cells are produced everyday. During erythropoiesis, nuclei are expelled from erythroid precursor cells and engulfed by macrophages. The failure of this process, the engulfment and degradation of apoptotic cells and nuclei, causes systemic lupus erythematosus (SLE)-type autoimmune disease and strong inflammation accompanied by anemia and polyarthritis. In this project, we will study the molecular mechanism how the inefficient engulfment and degradation of dead cells and nuclei cause the autoimmune disease and inflammation.

Mechanis of organ specific inflammatory/autoimmune diseases and the development of its control approach

Researcher's name Toshio Hirano
Research Site Professor, Osaka University
URL http://www.med.osaka-u.ac.jp/pub/molonc/www/index.html
Content We recently showed dysregulation of an IL-17-triggered positive feedback loop of IL-6 signaling, which involves the activation of NF-kB and STAT3 in fibroblasts, plays a role for arthritis development in mutant mice. Because this mechanism appears to enhance experimental autoimmune encephalomyelitis in wild-type mice, it might be a general etiologic process underlying other Th17 cell-mediated autoimmune diseases as well as chronic inflammatory diseases. In this project, our research is focused on analyzing in vivo homeostasis of the IL-6 loop on the molecular level to identify several molecular targets to efficiently control the enhancing level of the loop in vivo.

Main Research Collaborators list

Murakami, Masaaki Associate Professor, Osaka University

A novel strategy for treatment of immune-related disorders by using cytoskeleton regulating signals as targets

Researcher's name Yoshinori Fukui
Research Site Professor, Kyushu University
URL http://www.bioreg.kyushu-u.ac.jp/iden/
Content Remodeling of the actin cytoskeleton regulates many cellular functions in the immune system. The CDM family of proteins, evolutionarily conserved guanine nucleotide exchange factors, induce cytoskeletal reorganization by functioning downstream of various receptors. In this study, we will analyze comprehensively the structure, function and signal transduction of the CDM family proteins to identify chemical or natural compounds that inhibit effectively immune responses. This accomplishment will lead to the development of new therapeutics for intractable diseases such as autoimmune diseases and graft rejection.

Main Research Collaborators list

Yokoyama, Shigeyuki Project Director, RIKEN Yokohama Institute
Mutoh, Seitaro Corporate Executive, Astellas Pharma Inc.

Reprograming of immune system by modulation of intracellular signal transduction

Researcher's name Akihiko Yoshimura
Research Site Professor, Keio University School of Medicine
URL http://www.immunoreg.jp/
Content Helper T cell is known as a commander of immunity. After activation by antigenic stimulation, naïve helper T cells differentiate into either effector T cells responsible for positive immune reactions or regulatory T cells necessary for the negative regulation of immunity. Dysregulation of the balance between effector and regulatory T cells causes immunological disorders such as allergy and autoimmune diseases. We have discovered SOCS family proteins, which play pivotal roles in keeping such balance. In this project, we will further elucidate molecular mechanisms for the maintenance and regulation of helper T cell differentiation. Furthermore, we will develop new methods for reprogramming helper as well as memory T cells: conversion of effector and memory T cells into regulatory T cells, which will be a novel strategy for the regulation of immunological diseases.
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