| Budget Amount *help |
¥594,100,000 (Direct Cost: ¥457,000,000、Indirect Cost: ¥137,100,000)
Fiscal Year 2007: ¥81,900,000 (Direct Cost: ¥63,000,000、Indirect Cost: ¥18,900,000)
Fiscal Year 2006: ¥93,600,000 (Direct Cost: ¥72,000,000、Indirect Cost: ¥21,600,000)
Fiscal Year 2005: ¥93,600,000 (Direct Cost: ¥72,000,000、Indirect Cost: ¥21,600,000)
Fiscal Year 2004: ¥166,400,000 (Direct Cost: ¥128,000,000、Indirect Cost: ¥38,400,000)
Fiscal Year 2003: ¥158,600,000 (Direct Cost: ¥122,000,000、Indirect Cost: ¥36,600,000)
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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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