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Professor W. (Willem) van Eden, PhD

Thursday 12 December 2013

Prof.dr Willem van Eden
Department of Immunology / Infectious Diseases, University Utrecht

The group of Femke Broere, Ruurd van der Zee and Willem van Eden is interested in immuno-regulation and vaccines.
The fundamental problem in autoimmune conditions, is faulty regulation of the inflammatory process. It was once thought that the pathogenesis of autoimmune inflammation was initiated by the accidental emergence of a forbidden clone of self-reactive effector T cells; however, it is now clear that the immune systems of healthy people are populated with T cells and B cells bearing receptors that can bind self-antigens. Chronic inflammation and autoimmune diseases result from the chronic activation or repeated reactivation of self-reactive lymphocytes that are already resident in the cord blood at birth. Inflammatory disease results from the failure of the immune system to down-regulate its own potentially dangerous cells. Thus, the rational goal of therapy in diseases of unregulated inflammatory activation is to reinstate physiological regulation. Competing technologies, such as anti-CD3, CTLA4-Ig, anti-TNFα or B cell depleting antibodies, are oriented towards indiscriminate suppression of immune cells and molecules and are therefore less safe, more costly in side effects and do not provide adequate therapy of the basic condition.

In 1988 van Eden and colleagues discovered the role of stress proteins in self-tolerance. This serendipitous finding was published in Nature and was for two years in the top-100 of mostly cited paper in the biomedical domain. Resulting from this original finding are still current activities of this group directed towards development of an immuno-modulatory vaccine against rheumatoid arthritis on the basis of heat shock proteins. The group is also involved with Trajectum Pharma, which is a University of Utrecht derived spin-off company, which is aiming for the development of immuno-modulatory vaccines for humans.

Current research involves:
A. The selection of immuno-regulatory compounds and vaccine adjuvants in a transgenic mouse model system with a monoclonal T cell repertoire with specificity for a HSP70 derived immuno-regulatory peptide
B. Research in the area of safety of human vaccines. For this in vitro assays are developed, which have predictive value with respect to immunogenicity and safety. This work is done in the framework of a large European consortium (EU IMI).
C. In collaboration with various food industries the group is investigating the immuno-regulatory qualities of food ingredients. This is done in designed reported cell line systems, in primary human cell lines and in animal models of autoimmunity.

Current group members:
Dr. Femke Broere
Dr. Ruurd van der Zee
Drs. Susan van Aalst (AIO)
Drs. Marit de Groot (AIO)
Drs. Bram Margry (AIO)
Drs. Charlotte de Wolf (AIO)
Ing. Peter van Kooten (technician)
Dr. Aad Hoek (technician)
Dr. Irene Ludwig (technician)
Prof. Dr. Willem van Eden

Key publications:
van Eden W, van Herwijnen M, Wagenaar J, van Kooten P, Broere F, van der Zee R. Stress proteins are used by the immune system for cognate interactions with anti-inflammatory regulatory T cells. FEBS Lett. 2013 Jun 27;587(13):1951-8.

van Herwijnen et al. Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis PNAS 2012;109(35):14134-9

Keijzer C, Wieten L, van Herwijnen M, van der Zee R, Van Eden W, Broere F.Heat shock proteins are therapeutic targets in autoimmune diseases and other chronic inflammatory conditions. Expert Opin Ther Targets. 2012 Sep;16(9):849-57

Berlo SE et al , Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice. Arthritis Rheum. 2006; 54: 2423-33.

van Puijvelde GH, et al. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation. 2006; 114: 1968-76.

van Eden W, van der Zee, Prakken B. Heat-shock proteins induce T-cell regulation of chronic inflammation. Nature Reviews Immunology 2005; 5, 318-330.

Anderton, S.M., Zee, R. van der, Prakken, B., Noordzij, A. & Eden, W. van (1995). Activation of T cells recognizing self 60kDa heat shock protein can protect against experimental arthritis. J. Exp. Med. 181: 943-952 (1995).

Broeren, C.P.M., Lucassen, M.A., Stipdonk, M.J.B. van, Zee, R. van der, Boog, C.J.P., Kusters, J.G. & Eden, W. van (1994). CDR1 T-cell receptor -chain peptide induces MHC class-II restricted T-T cell interactions. PNAS USA 91: 5997-6001 (1994).

Wauben, W.H.M. , Boog, C.J.P., Zee, R. van der, Joosten, I., Schlief, A. & Eden, W. van (1992) Disease inhibition by Major Histocompatibility Complex binding peptides analogues of disease associated epitopes: More than blocking alone. J. Exp. Med. 176: 667-677 (1992).

Eden, W. van et al. (1988), "Cloning of the mycobacterial epitope recognised by T lymphocytes in adjuvant arthritis", Nature 1988, 331: 171-73. This paper was in 1989 and 1990 among the top-100 most cited papers worldwide in the Life Sciences. [Garfield, Current Contents 48 (1990), 5-19].

Van Eden W, Wick G, Albani S, Cohen I. Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann N Y Acad Sci. 2007;1113:217-37. Review