Reumatologie - Molecular Immunology and Inflammation

Medewerkers

Staf:

Prof. dr. Dirk Elewaut

Postdoctorale medewerkers:

dr. sc. Koen Venken

dr. sc. Michael Drennan

dr. sc. Stijn Lambrecht

dr. sc. Els Louagie

Doctorandi:

Sylvie Seeuws

dr. Peggy Jacques

dr. Sandrine Aspeslagh

dr. Jens Van Praet

Lode Melis

dr. Aad Dhollander

Technische medewerkers:

Nele Degryse

Tine Decruy

Julie Coudenys

Carine Broddelez

Eveline Verheugen

Onderzoeksprojecten

Onderzoeksproject 1: 1. Role of Natural Killer T (NKT) cells in health and disease.

 
The aim of this programme is to examine the biology of NKT cells with special emphasis on differentiation and their role in experimental arthritis and ileitis. NKT cells form a unique lymphocyte subset with important immunoregulatory properties because of the large quantities of both Th1 and Th2 cytokines they produce (notably IFN-γ, IL-4 and IL-10) upon TCR stimulation. Some subsets may also produce IL-17. These cytokines  can influence the function of other immune cells such as NK cells and conventional T lymphocytes. We have previously reported that lymphotoxin (LT)αβ, a member of the immediate TNF cytokine family, plays a unique role in the ontogeny of NKT cells by influencing the emigration of NKT cells, but not of conventional T cells, from the thymus to peripheral organs. Our current focus is to delineate the molecular pathways regulating this thymic export in vitro and in vivo to understand why the emigration pathways of NKT cells are distinct from mainstream T cells. This includes several approaches such as chemotaxis assays, genomics studies and cell fate mapping experiments.  In addition, we are examining the role of other members of the TNF family on NKT cell function, homeostatic expansion and survival and their impact on the course of inflammatory disorders such as collagen induced arthritis, a murine model of antigen induced arthritis and TNFΔARE mice, a model of spondyloarthritis. Other strategies to influence NKT cell function such as the generation of altered glycolipid antigens to differentially stimulate NKT cells in order to optimize the induced cytokine pattern (Th1 versus Th2 bias) are also explored (in collaboration with Prof. S. Van Calenbergh (Faculty of Pharmaceutical Sciences).


Onderzoeksproject 2: Cellular and molecular mechanisms  of joint inflammation.


The aim of this project is to characterize the distinctive features of synovial inflammation in two of the most frequent forms of chronic arthritis, rheumatoid arthritis (RA) and spondyloarthropathy (SpA), and the mechanisms underlaying cytokine mediated cartilage damage. Although the clinical presentation of these diseases is distinct, relatively little is known about the molecular differences in the underlying synovitis. Different complementary approaches are currently ongoing. The first involves proteomics and was initiated by a differential screening approach using a high resolution 2-dimensional gelectrophoresis combined with tandem mass spectometry (in collaboration with the group of Prof. Deforce, Faculty of Pharmaceutical Sciences). In different forms of chronic synovitis, the protein expression patterns appeared be distinct. We extended this to human chondrocytes in health and under catabolic conditions. Differentially expressed proteins include proteins involved in cell metabolism, cell survival, cell motility, heat shock proteins and novel proteins with yet unknown functions. Of interest, some intermediate filaments appear to undergo proteolysis and posttranslational modifications, which are associated with the development of autoantibodies with a high specificity. This appears to occur in RA much more frequent than in SpA. Another approach aims to investigate the effector functions of fibroblast like synoviocytes in chronic synovitis, a key cell type in mediating inflammation and cartilage damage. Finally, we are studying the in vivo effects of various anti-inflammatory compounds on the occurrence and severity of joint inflammation in collagen induced arthritis.

Belangrijkste publicaties

Coppieters K, Van Beneden K, Jacques P, Dewint P, Vervloet A, Vander Cruyssen B, Van Calenbergh S, Chen G, Franck RW, Verbruggen G, Deforce D, Matthys P,  Tsuji M, Rottiers P, Elewaut D.   A Single Early Activation of Vα14i Natural Killer T cells Confers Long-Term Protection Against Collagen-Induced Arthritis in a Ligand Specific Manner. J Immunol, 2007; 179(4):2300-9.

Franki AS, Van Beneden K, Dewint P, Hammond KJ, Lambrecht S, Leclercq G, Kronenberg M, Deforce D, Elewaut D. A unique lymphotoxinαβ-dependent pathway regulates thymic emigration of Vα14 invariant natural killer T cells. Proc Natl Acad Sci U S A, 2006; 103(24):9160-5.

Elewaut D, Ware CF  The unconventional role of LTalphabeta in T cell differentiation.  Trends Immunol, 2007; 28(4):169-75.

Dewint P, Gossye V, De Bosscher K, Vanden Berghe W, Deforce D, Van Calenbergh S, Müller-Ladner U, Vander Cruyssen B, Verbruggen G, Haegeman G, Elewaut D. A plant-derived ligand favouring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis. J Immunol, 2008; 180(4):2608-15.

Armaka M, Apostolaki M, Jacques P, Kontoyiannis D, Elewaut D and Kollias G. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med, 2008; 205(2):331-7.

Van Beneden K, Coppieters K, Laroy W, De Keyser F, Hoffman IE, Van den Bosch F, Vander Cruyssen B, Rottiers P, Verbruggen G, Contreras R, Callewaert N, Elewaut D.  Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory auto-immune arthritis. Ann Rheum Dis, 2009; 68(8):1360-5.

Trappeniers M, Beneden KV, Decruy T, Hillaert U, Linclau B, Elewaut D, Calenbergh SV. 6'-Derivatised alpha-GalCer Analogues Capable of Inducing Strong CD1d-Mediated Th1-Biased NKT Cell Responses in Mice. J Am Chem Soc, 2008; 130(49):16468-9.

Jacques P, Elewaut D.  Joint expedition: linking gut inflammation to arthritis. Mucosal Immunol, 2008 Sep; 1(5):364-71.

Drennan, MB, Franki AS, Dewint P, Van Beneden K, Seeuws S, van de Pavert SA, Reilly EC, Verbruggen G, Lane TE, Mebius RE, Deforce D and Elewaut D. Cutting Edge: The chemokine receptor CxCR3 retains invariant natural killer T cells in the thymus J Immunol, 2009; 183(4):2213-6.

Gossye V, Elewaut D, Bougarne N, Bracke D, Serge Van Calenbergh S, Haegeman G, De Bosscher K. Differential mechanism of nuclear factor-kappa b inhibition by two GR modulators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum, 2009; 60(11):3241-3250.

Lambrecht S, Dhaenens M, Almqvist F, Verdonk PC, Deforce D, Elewaut D. Proteome characterization of human articular chondrocytes leads to novel insights in the function of small heat-shock proteins in chondrocyte homeostasis Osteoarthritis Cartilage.

Jacques P, Venken K, Van Beneden K, Hammad H, Seeuws S, Drennan MB, Deforce D, Verbruggen G, Apostolaki M, Kollias G, Lambrecht B, De Vos M, Elewaut D. Invariant Natural Killer T cells are natural regulators of spondyloarthritis. Arthritis Rheumatism, 2009.

Drennan MB, Aspeslagh S, Elewaut D. Invariant natural killer T cells in rheumatic disease: a joint dilemma. Nat Rev Rheumatol, 2009.

Volledige publicatielijst