Molecular and functional characterization of the novel cytokine IL-35

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

We have recently reported the finding of a new protein called IL-35 which can potently suppress experimental rheumatoid arthritis. We now wish to exploit this discovery and translate it into clinical applications. To do so, we need to know much more about the characteristic of this molecule. This project is designed to do so. We have assembled a team of experts in the fields of molecular biology, cellular immunology and clinical trials, together with international collaborations. We hold intellectual property right to IL-35 and are in negotiation with a biotech company to develop IL-35 as a therapeutic reagent. We believe that this project will not only lead to greater understanding of the basic knowledge of how our immune system works but also to a potent therapeutic agent against some of the major diseases impacting on global health and economy.

Technical Summary

We have recently reported (1) the finding of the novel cytokine, IL-35, which enhanced the proliferation of regulatory T (Treg) cells and suppressed the development of Th17. Furthermore, IL-35 attenuated collagen-induced arthritis in mice and was detected in the diseased-joints of patients with rheumatoid arthritis (RA). IL-35 was also recently reported to be produced by Treg cells (2). Thus IL-35 represents an exciting novel therapeutic agent against a range of inflammatory diseases. However, little is known about the molecular mechanism of action and its role in other diseases. We propose here to investigate the molecular nature of IL-35 in vivo, IL-35 receptor and the signaling pathway of IL-35. We will also explore the role of IL-35 in a number of key infection and inflammatory disease models. Finally, we will investigate the role of IL-35 in clinical RA. We have assembled a team of leading experts in the fields of molecular, cellular and system biology to focus on this project, together with international collaborators who are specialists in the field of infection and inflammation. We will employ the latest technologies available, including gene targeting, cell imaging, siRNA and proteomics. We also have extensive clinical trial facilities and experience and we hold the intellectual property right of IL-35 and have a close working relationship with a biotech company. Thus, this project could rapidly lead to clinical applications of IL-35 to some of the major infectious and inflammatory diseases.

Publications

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Gabriele L (2013) Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen. in The Journal of allergy and clinical immunology

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Hueber AJ (2011) IL-33 induces skin inflammation with mast cell and neutrophil activation. in European journal of immunology

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Jiang HR (2009) Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. in Journal of immunology (Baltimore, Md. : 1950)

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Komai-Koma M (2009) Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex. in European journal of immunology

 
Description MRC
Amount £235,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 08/2010 
End 07/2013