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Sub theme 2.5
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Workgroup leaders | Department | |
prof.dr P.A. van Doorn | Neurology | |
Prof.dr. H.A. Drexhage | Immunology | |
pro.dr. B.C. Jacobs | Neurology | |
Dr. P.J.M. Leenen | Immunology | |
Dr. V.H.J. van der Velden | Immunology |
Goals of research: general outline |
The Dept. of Immunology focuses on lymphatic and myeloid differentiation, immune regulation and inflammation. Chronic inflammation and autoimmune disease are leading causes of morbidity, psycho-siocal burden and economic loss in Western societies. In view of the central role of innate and adaptive immunity in these diseases, detailed insight into immune regulation is a requirement for elucidation of the immune pathogenesis of chronic inflammatory and autoimmune processes and the rational development of diagnostics and immune therapy. The Postgraduate School Molecular Medicine has an extensive and active program in immune regulation and autoimmunity, consisting of a close collaboration between clinical and pre-clinical departments. Chronic inflammatory diseases of interest are type I diabetes, thyroiditis, affective disorders and schizophrenia (all having a major immuno-neuro-endocrine component), rheumatoid arthritis (RA) and the related disorder Sjögren’s disease, psoriasis, and the demyelinating diseases multiple sclerosis (MS) and Guillain-Barré syndrome (GBS). The general premise is that the immune mechanisms driving the multi-factorial pathological processes in these different diseases of interest are highly analogous. Our overall aims within the frame of aforementioned diseases are to unravel:
Research topics include basic immune pathogenic mechanisms (e.g. molecular mimicry in GBS and MS); immune-endocrine interactions (e.g. in the pathogenesis of postpartum thyroiditis and psychosis and in the linked amelioration of MS, thyroiditis and RA during pregnancy); molecular signaling pathways in chronic autoimmune inflammation (e.g. transcription factors in psoriasis and major psychiatric diseases, inflammatory gene signature expression in monocytes in major psychiatric and autoimmune diseases, epi-genetic regulation of these various genes); experimental immune therapy (e.g. antibodies against co-stimulatory molecules and cytokines); immune regulation by external factors (e.g. UV irradiation and skin inflammation, infection and MS activity); immune function and disease activity in MS; and immune dysregulation by aberrant development and activity of antigen presenting cells (e.g. in diabetes, Sjögren’s syndrome, thyroiditis, atherosclerosis, affective disorders, schizophrenia and histiocytosis). Team Close collaboration with clinical researchers who are well trained in immunology allows joint elaboration of scientifically relevant research questions, construction of well-characterized patient cohorts, and evaluation of experimental immune therapies. Specifically, the departments of Neurology (workgroup leaders Prof.Dr. R.Q. Hintzen, Dr. B.C. Jacobs, Prof.Dr. P.A. van Doorn), Dermatology (Prof.Dr. H.A.M. Neuman, Prof.Dr. E.P. Prens), Rheumatology (Prof.Dr. J.M.W. Hazes, Dr. E. Lubberts, Dr. R.J.E.M. Dolhain) and Internal Medicine (Dr. P.M. van Hagen) have integrated their immune research within this research line of the Molmed School. There is additional close collaboration on the role of microbial compounds in immune regulation with the departments of Virology (Prof.Dr. A.D.M.E. Osterhaus), Medical Microbiology and Infectious Diseases (Prof.Dr. H.A. Verbrugh, Dr. H.P. Endtz, Prof.Dr. A. van Belkum). Furthermore, the departments of Internal Medicine (Prof.Dr. A.J. van der Lely, Prof.Dr. T.J. Visser) and Immunology collaborate on thyroid autoimmune disease and on diabetes, and the departments of Psychiatry (Prof.Dr. S. Kushner, Dr. V. Bergink, Dr. J.M. van Beveren) and Immunology on immune aberrancies in major affective disorders and schizophrenia. In addition, long-standing collaborations exist with the department of Genetics (Prof.Dr. J.H.J. Hoeymakers, Dr. J. Pothof) on UV-mediated effects on immunity and microRNA regulation of gene expression. Combining researchers with different backgrounds (e.g. the clinic, molecular biology, cellular immunology) working on these different diseases in a single integrated team significantly stimulates scientific discussion and output. The joint expertise allows coverage of a broad area of approaches and technology, ranging from patient cohort studies via functional in vitro and genetic analyses of patient material to several animal disease models in rodents and non-human primates including the generation of novel (conditional) transgene and knockout mouse models. |
Scientific achievements |
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Future plans: special goals and approach |
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Most recent publications |
1. Padmos RC, Schloot NC, Beyan H, Ruwhof C, Staal FJ, de Ridder D, Aanstoot HJ, Lam-Tse WK, de Wit H, de Herder C, Drexhage RC, Menart B, Leslie RD, Drexhage HA; LADA Consortium. Distinct monocyte gene-expression profiles in autoimmune diabetes. Diabetes 2008; 57:2768-73. 2. Padmos RC, Hillegers MH, Knijff EM, Vonk R, Bouvy A, Staal FJ, de Ridder D, Kupka RW, Nolen WA, Drexhage HA. A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry. 2008; 65:395-407. 3. van Koningsveld R, Steyerberg EW, Hughes RAC, Swan AV, van Doorn PA, Jacobs BC. A clinical prognostic scoring system for Guillain-Barré syndrome. Lancet Neurol 2007;6:589-94. 4. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis and treatment of Guillain-Barré syndrome. Lancet Neurol 2008;7:939-50. 5. Bennett CL and Clausen BE. Dendritic cell ablation in mice: promises, pitfalls and challenges. Trends Immunol. 2007; 28:519-25. 6. Bennett CL, Noordegraaf M, Martina CA, Clausen BE. Langerhans cells are required for efficient presentation of topically applied hapten to T cells. J Immunol. 2007; 179:6830-5. 7. Boven LA, van Meurs M, van Zwam M, Wierenga-Wolf A, Hintzen RQ, Boot RG, Aerts JM, Amor S, Nieuwenhuis EE, Laman JD. Myelin-laden macrophages are anti-inflammatory consistent with foam cells in multiple sclerosis. Brain 2006; 129:517-26. 8. ‘t Hart BA, Hintzen RQ, Laman JD. Multiple sclerosis, a response-to-damage model. Trends Mol Med. 2009; 15:235-44. 9. Hintzen RQ, Giovannoni G. CSF analysis in suspected MS: do bands aid? Neurology 2008; 70:1059-60. 10. Neuteboom RF, Boon M, Catsman Berrevoets CE, Vles JS, Gooskens RH, Stroink H, Vermeulen RJ, Rotteveel JJ, Ketelslegers IA, Peeters E, Poll-The BT, De Rijk-Van Andel JF, Verrips A, Hintzen RQ. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 2008; 71:967-73. 11. de Lau LM, de Vries JM, Kuipers E, van der Woude CJ, Kuipers EJ, Siepman DA, Sillevis Smitt PA, Hintzen RQ. Acute CNS white matter lesions in patients with inflammatory bowel disease. Inflammatory Bowel Diseases 2009; 15:576-80. 12. Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJM. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol. 2004; 172:4410-7. 13. Cheng C, Tempel D, van Haperen R, de Boer HC, Segers D, Huisman M, van Zonneveld AJ, Leenen PJM, van der Steen A, Serruys PW, de Crom R, Krams R. Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines. J Clin Invest. 2007; 117:616-26. 14. Wildenberg ME, van Helden-Meeuwsen CG, van de Merwe JP, Drexhage HA, Versnel MA. Systemic increase in type I interferon activity in Sjögren's syndrome: a putative role for plasmacytoid dendritic cells. Eur J Immunol. 2008;38:2024-2033. |