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| Collaborative institutes Laboratory of Immune Regulation Chugai Pharmaceutical CO., LTD. |
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| Professor |
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+81-6-6879-4431 |
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+81-6-6879-4437 |
| Associate Professor |
Shigemi Kinoshita, PhD. |
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| Assistant Professor |
Akihiro Kimura, PhD. |
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+81-6-6879-4432 |
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Interleukin-6 (IL-6)?
IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively by the common signal-transducing component gp130, which is also essential for signal transduction of other cytokines of the leukemia inhibitory factor (LIF)/IL-6 family. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease.
Regulatory system of IL-6 in Treg/Th17 development?Recently, a new subset of Th cells producing IL-17 (Th17) has been identified and shown to have a crucial role in the induction of autoimmune diseases such as rheumatoid arthritis and experimental autoimmune encephalomyelitis (EAE) as well as allergen-specific responses. Th17 cells differentiation is driven by the combination of IL-6 and TGF-?, whereas IL-6 inhibits the development of regulatory T (Treg) cells by TGF-?. Our current research is focused on demonstrating how IL-6 controls the generation of Treg/Th17 cells.
We not only revealed the framework of cytokine signaling, including identification of the IL-6 receptor, gp130, NF-IL6, STAT3, and SOCS-1, but also led to the development of a new therapy for chronic inflammatory diseases. Recent studies demonstrated that Th17, distinct from Th1 and Th2, is the main pro-inflammatory CD4+ effector T cell involved in CIA and EAE. Understanding the precise mechanisms of Th17 differentiation by IL-6 will lead to resolve the immune disorder that causes immune-mediated inflammatory diseases.
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