Regulation of Immune responses and autoimmune diseases by cytokines

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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.