The gut is a vital organ for both mucosal and systemic immune homeostasis. Dysregulated immune responses towards the normal intestinal flora underlie a myriad of gastrointestinal diseases s.a. Crohn’s disease and ulcerative colitis, but are also linked to extra-intestinal pathologies. We study the mechanisms of inflammation and associated tissue damage (cartilage/bone) occurring in musculoskeletal diseases, particularly spondyloarthritis (SpA), osteoarthritis and rheumatoid arthritis, and how these mechanisms are regulated by intestinal immunity. The lab discovered that spondyloarthritis (SpA) patients 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.
The MIIT lab is strongly linked with the clinic (Prof. Elewaut is head of the Rheumatology Department at the Ghent University hospital) and is evaluating gut samples from an ongoing prospective cohort study, the Ghent Inflammatory Arthritis and spoNdylitis cohort (GIANT). This cohort is composed of new- onset SpA-patients receiving an extensive baseline investigation including X-ray analysis, ileocolonoscopy, gut and ilial biopsies, stool and serum isolation. Patients are followed every 6 months systemically for at least 10 years (started in 2010). MIIT recently discovered the over-abundance of the bacterial genus Dialister in the microbiota of ileum and colon of SpA patients from the GIANT cohort and linked Dialister with disease activity.
In addition to studying the gut-joint axis, the MIIT lab has a longstanding interest in the biology of iNKT cells under steady state conditions and in arthritic disease. Other research lines in the MITT lab focus on the link between mechanical strain and musculoskeletal disorders, and on ways to restore joint homeostasis by modulating cartilage and bone metabolism (joint remodeling).
A unique feature of MIIT’s research is the “reverse translational approach” where initial discoveries and observations in well-characterized patients’ cohorts, are translated to to deep mechanistic studies using in vitro models and unique mouse models of arthritic disease. This will result in a reiterative loop of translational research, generating new targets and concepts that open novel perspectives for future therapeutic interventions.