Dirk Elewaut Lab

Research focus

​Our unit studies the mechanisms of inflammation and associated tissue damage (cartilage/bone) occurring in musculoskeletal diseases, particularly spondyloarthritis (SpA), osteoarthritis and rheumatoid arthritis  using a translational research approach. Areas of specific interest include:

1. Gut inflammation as a driver of joint inflammation in SpA: we found that patients presenting to rheumatologists with a clinical presentation of SpA have in about 50% microscopical evidence of bowel inflammation unrelated to clinical gastrointestinal symptoms. “Subclinical” bowel inflammation is associated with long-term outcome of joint symptoms: gut inflammation is linked to more extensive disease (more severe joint symptoms, more spinal inflammation), but also represents an important risk factor for development of full blown Crohn’s disease. In a collaborative study, we showed mesenchymal cells to be crucial effector cells in the gut-joint axis in SpA. Regulatory cells by contrast, particularly invariant natural killer T (iNKT) cells, have a marked anti-inflammatory effect. There is recent evidence that iNKT cells recognize glycolipids derived from gut microbiota. Therefore, one of our current goals is to understand how regulatory cells are affected by alterations of gut microbiome in SpA.

2. Promoting immunoregulation in arthritic disease: We have a longstanding interest in the biology of iNKT cells under steady state conditions and in arthritic disease. These innate-like T cells are attractive targets: highly conserved across mammalian species including humans, ability to rapidly respond to antigens by producing copious amounts of Th1, Th2 and some subsets Th17 cytokines which cause an important bystander immune activation. There is a marked flexibility of this system; by altering structure of glycolipid antigens, NKT cell responses can be skewed toward polarized Th responses. We showed that even a single administration of strong NKT cell agonists is able to markedly attenuate collagen induced arthritis, a mouse model of rheumatoid arthritis. In collaboration, we generated new synthetic ligands for iNKT cells that are structural variants of a prototypical ligand -GalCer which induces a mixed Th1/Th 2 profile. Our compounds are very potent Th1 biasing iNKT agonists, and we unravelled the molecular basis by solving crystal structures of CD1d-glycolipid-NKT T cell receptor complexes. The modifications introduced on our ligands favor stronger interactions with either CD1d or the iNKT T cell receptor, leading to more robust calcium fluxes and sustained downstream signalling. We have also uncovered an important functional interaction between Treg cells and iNKT cells that is dependent upon the nature of iNKT stimulation. Thus, iNKT cell responses are tightly controlled by an immune regulatory feedback loop. Our current research is focused around understanding chronicity of arthritic disease and particularly why regulatory feedback mechanisms fail in arthritic disease.

3. Mechanical strain: a common pathogenic principle for musculoskeletal disorders. A longstanding question in the field of rheumatology is how systemic inflammatory diseases localize to joint tissues. For example, a prototypical musculoskeletal manifestation of SpA is enthesitis, inflammation at the insertion of tendons. We hypothesized that mechanical strain could be an important factor. More precisely we anticipated that SpA patients would react abnormally to normal physiological stress occurring during biomechanical loading. We addressed this paradigm shifting idea in mice by hindlimb unloading experiments in a mouse model of SpA characterized by enhanced TNF mRNA stability and spontaneous development of enthesitis. Unloading inhibits enthesitis development entirely We also showed using another model that new bone formation, an additional feature of SpA, is equally dependent upon mechanical strain. Mechanistically, the ERK MAPK pathway is at least partially responsible for this. Currently, we are performing a number of additional studies to study molecular mechanisms driving this.

4. Restoring joint homeostasis by modulating cartilage and bone metabolism (joint remodeling). Chronic inflammation and mechanical strain are accompanied by rapid degradation of articular cartilage which is a vulnerable target for catalytic and proteolytic enzymes. Additionally, activation of osteoclasts affects bone integrity locally but also systemically. These catabolic processes are also implicated in osteoarthritis. Over the past years, we have established several new modes to influence human chondrocyte metabolism and to monitor their stability, essential for proper matrix synthesis.  We also study new modes of modulation of osteoclast formation in steady state or under conditions of chronic inflammation, a particularly high risk factor for inflammation induced bone loss.


Ankle joint  
© Dirk Elewaut, 2015
© Dirk Elewaut, 2015



A20 inhibition of STAT1 expression in myeloid cells: a novel endogenous regulatory mechanism preventing development of enthesitisDe Wilde K, Martens A, Lambrecht S, Jacques P, Drennan M, Debusschere K, Govindarajan S, Coudenys J, Verheugen E, Windels F, Catrysse L, Lories R, Mcgonagle D, Beyaert R, van Loo G, Elewaut DANNALS OF THE RHEUMATIC DISEASES, 76, 585-592, 2017
Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myelomaFavreau M* Menu E* Gaublomme D* Vanderkerken K Faict S Maes K De Bruyne E Govindarajan S Drennan M Van Calenbergh S Leleu X Zabeau L Tavernier J Venken K* Elewaut D*LEUKEMIA, e-pub, e-pub, 2017* These authors contributed equally
NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20Drennan M* Govindarajan S* Verheugen E Coquet J Staal J Mcguire C Taghon T Leclercq G Beyaert R Van Loo G Lambrecht B* Elewaut D*JOURNAL OF EXPERIMENTAL MEDICINE, 213, 1973-81, 2016* These authors contributed equally
How the microbiota shapes rheumatic diseasesVan De Wiele T, Van Praet J, Marzorati M, Drennan M, Elewaut DNature Reviews Rheumatology, 12, 398-411, 2016
Commensal microbiota influence systemic autoimmune responsesVan Praet J* Donovan E* Vanassche I Drennan M Windels F Dendooven A Allais L Cuvelier C Van De Loo F Norris P Kruglov A Nedospasov S Rabot S Tito-Tadeo R Raes J Gaboriau-Routhiau V Cerf-Bensussan N Van De Wiele T Eberl G Ware C Elewaut DEMBO JOURNAL, 34, 466-74, 2015* These authors contributed equally

Job openings


Scientists give tumor-fighting cells a boost in battling bone marrow cancer

01/06/2017 - Researchers led by Prof. Dirk Elewaut and the team of Prof. Vanderkerken and Prof. Menu at the Hematology and Immunology lab of the VUB uncovered a new way to enhance the function of a specific type of immune cell that destroys tumors in multiple myeloma

Ghent-based researchers are the cream of the crop in rheumatology

28/01/2017 - As an umbrella term, rheumatism covers dozens of specific diseases of the muscles, joints and bones – which require different treatments. Because an overall cure remains undiscovered, patients and their associations are placing their hopes in science.

Belgian rheumatology researchers are among Europe’s finest

19/09/2016 - For the third time in a row, an alliance of Ghent-based researchers & clinicians has been awarded the label EULAR Center of Excellence. This European institute fosters excellence in education and research in the field of rheumatology.

Research opens up new treatment route for inflammatory rheumatism

23/08/2016 - ​Chronic tendinitis is a common medical problem which underlies various forms of inflammatory rheumatism. Although around 1% of the population is affected, the pathogenesis of such inflammatory conditions has not yet been explained.

Dirk Elewaut

Dirk Elewaut

Research area(s)

Model organism(s)


PhD: Ghent Univ., Ghent, Belgium, 1997
Postdoc: Univ. of California, San Diego, USA, 1997-98
Postdoc: La Jolla Inst. for Allergy & Immunology, San Diego, USA, 1998-99
Professor of Medicine: Ghent Univ., Ghent, Belgium since 2008
VIB Group leader as of January 2015

Contact Info

VIB-UGent Center for Inflammation ResearchUZ GentDe Pintelaan 185 9000 GENT