16:00 - 18:00
Room: ANA Crowne Plaza “Ohtori” Room B
Keynote Lecture
Chair/s:
Akihiko Yoshimura, Kouji Matsushima, Tadatsugu Taniguchi
From the discovery of IL-6 to the development of anti-IL-6R anti body.
Tadamitsu Kishimoto
Laboratory of Immune Regulation, Immunology Frontier Research Center, Osaka University, Osaka, Japan

A series of our studies in IL-6 have revealed that it has a pleiotropic activity in various tissues and cells and its deregulated expression is responsible for several chronic inflammations and hemopoietic malignancies.

Humanized antibody against 80kd IL-6R (Tocilizumab) has shown significant therapeutic effect in RA, JIA, Castleman’s diseases and several other autoimmune inflammatory diseases, such as progressive sclerosis, giant cell arteritis, reactive arthritis, polymyalgia rheumatica and adult still’s desease. Cytokine storm induced by hyper activation of T cells has been shown to be controlled by Tocilizumab. Recently, TH17 is shown to be responsible for the pathogenesis of autoimmune diseases and IL-6 together with TGF-b are essential for the induction of TH17. We identified a new transcription factor required for Th-17 cell induction. This molecule, aryl hydrocarbon receptor (Ahr) interacts with Stat1 and Stat5 and abrogate their negative activity in the induction of Th-17 cell differentiation. Experimental arthritis is completely abrogated in T cell-specific Ahr-deficient mice.

Therapeutic effect of Tocilizumab confirmed that over and constitutive-production of IL-6 is responsible for the pathogenesis of autoimmune diseases.

Then, the question to be asked is how is IL-6 production regulated. We identified a novel molecule called Arid5a which binds with the 3’-UTR of IL-6 mRNA and protects its degradation by competing with Regnase-1. Interestingly, this molecule is present in nuclei and inflammatory stimulation induced translocation of Arid5a from nuclei into cytoplasm and it competes with Regnase-1 for the protection of mRNA of IL-6.

Arid5a binds with the 3’-UTR of not only IL-6mRNA but also STAT3 mRNA in TH17 cells as well as T-bet mRNA in TH1 cells. Thus, Arid5a accelerates Th17cell differentiation in inflammation as well as exacerbation of IFN-ɤ-mediated septic shock.

All these results indicate that Arid5a is one of the key molecules for inflammation as well as the development of septic shock.

The results also suggest the therapeutic potential of anti-agonistic agents for Arid5a in the prevention of various incurable inflammatory diseases and septic shock.


Reference:
Su-K-1
Session:
Opening Keynote Lectures 1-3
Presenter/s:
Tadamitsu Kishimoto
Presentation type:
Keynote Speaker
Room:
ANA Crowne Plaza “Ohtori” Room B
Chair/s:
Akihiko Yoshimura, Kouji Matsushima, Tadatsugu Taniguchi
Date:
Sunday, 29 October 2017
Time:
16:00 - 16:40
Session times:
16:00 - 18:00