2007 Fiscal Year Final Research Report Summary
Regulation of Immune responses and autoimmune diseases by cytokines
| Project/Area Number |
15002008
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
HIRANO Toshio Osaka University, Graduate School of Frontier Biosciences, Professor (40136718)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Masaaki Osaka University, Graduate School of Frontier Biosciences, Associate Professor (00250514)
YAMASHITA Susumu Osaka University, Graduate School of Frontier Biosciences, Assistant Professor (90346148)
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| Project Period (FY) |
2003 – 2007
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| Keywords | memory T cells / cytokine / homeostatic proliferation of T cells / Zinc / intracellular signaling / second messenger |
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| Research Abstract |
Our aim of this study was to know how Y759F mutation in gp130, an IL-6 signal transducer, induces an autoimmune arthritis disease in vivo and to investigate a role of IL-6-mediated signaling in the normal immune responses. We obtained two important concepts showing how tissue specific autoimmune diseases are induced as described below.
(1) Excess IL-7 expression induced by activation of non-hematopoietic cells via an excess IL-6 signaling triggers an excess homeostatic proliferation of CD4+ T cells followed by the development of autoimmune arthritis in F759 mice. We demonstrated how a dysregulated interaction between non-hematopoietic cells and hematopoietic cells, CD4+ T cells, induces a tissue specific autoimmune diseases in vivo.
(2) There is an IL-17-mediated IL-6 positive feedback loop in non-hematopoietic cells even in normal condition in vivo. Dysregulation of the IL-6 loop by a genetic abnormality such as Y759F mutation in F759 mice induces an excess production of IL-6 via the loop followed by the development of autoimmune arthritis.
Moreover, we proved the existence of intracellular Zinc signaling, which is also important for regulation of immune cell functions.
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[Presentation] Zinc signaling in dendritic cells2007
Author(s)
村上正晃
Organizer
The 20^<th> Naito Conference on Innate Immunity in Medicine and Biology [III]
Place of Presentation
Shonan Village Center, Kanagawa, Japan
Year and Date
2007-10-11
Description
「研究成果報告書概要(和文)」より
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[Presentation] Zinc and immunity_allergy2007
Author(s)
Hirano, T.
Organizer
The 19^<th> Spring Meeting of Japanese Society of Allergology, Special Program
Place of Presentation
Pacifico Yokohama, Japan.
Year and Date
2007-06-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Aberrant cytokine signaling and autoimmune disease.2007
Author(s)
Hirano, T.
Organizer
The 27^<th> General Assembly of The Japan Medical Congress, Special Lecture, Immune system and its disruption-For understanding higher complex immune system
Place of Presentation
Osaka International Convention Center, Japan.
Year and Date
2007-04-06
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Cytokines and rheumatism2005
Author(s)
Hirano, T.
Organizer
The 16^<th> Science Meeting of Kanto branch of Japan College of Rheumatology. Symposium 2 “From Immunobiology to Rheumatology"
Place of Presentation
Tsukuba International Congress Center, Japan.
Year and Date
2005-12-10
Description
「研究成果報告書概要(欧文)」より
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