Jeroen den Dunnen, PhD
Assistant Professor AMC
My group studies how antibodies and antibody receptors (Fc receptors) orchestrate inflammatory responses in a large variety of disorders, including bacterial and viral infections, autoimmune diseases, but also chronic inflammatory disorders such inflammatory bowel disease and chronic rhino sinusitis. With a background in molecular immunology (cell signaling by C-type lectins; publications in Immunity and Nature Immunology) I set up my own research group that studies antibody-induced inflammation at the Department of Cell Biology in the AMC in 2011.
One of our key initial findings was that we identified a new function of antibodies in shaping host defense during bacterial infections (Blood 2012). Later on we identified that antibody-induced inflammation also has a ‘dark side’, by strongly promoting inflammation in the context of rheumatoid arthritis (Nature Communications 2014). Considered the relevance of our research for rheumatic disorders, I moved my lab to the Department of Rheumatology in 2016, supported by prestigious personal grants such as the AMC Fellowship.
In recent years our research revealed that Fc receptor-induced inflammation is involved in a wide range of different diseases, including inflammatory bowel disease (Nature Communications 2018), chronic rhino sinusitis (Mucosal Immunology 2019), SLE (Clin Exp Immunol 2019), and multiple sclerosis (manuscript in prep.). Our collaborations with clinicians in all these different fields underline the strong multidisciplinary nature of the research in our group.
One of main current goals is to find new ways to therapeutically counteract Fc receptor-induced inflammation, which requires in depth knowledge of the underlying molecular mechanisms. Our most recent findings identified that Fc receptor-induced inflammation critically depends on metabolic changes at the cellular level (J Immunol 2019; Front Immunol 2019; Nat Commun 2018), a process known as ‘metabolic reprogramming’. By collaborating with experts in the field of (immuno)metabolism and state-of-the-art techniques we now aim to unravel the metabolic pathways that drive pathology in aforementioned diseases. In the ARCAID project we have two exciting vacancies that will focus on identifying these metabolic pathways in (1) rheumatoid arthritis and inflammatory bowel disease, and (2) during HIV infection.
Key recent publications of the Den Dunnen group:
- Dysregulated Fc gamma receptor IIa-induced cytokine production in dendritic cells of lupus nephritis patients. Newling M, Fiechter RH, Sritharan L, Hoepel W, van Burgsteden JA, Hak AE, van Vollenhoven RF, van de Sande MGH, Baeten DLP, den Dunnen J. Clin Exp Immunol. 2019 accepted for publication.
- C-Reactive Protein Promotes Inflammation through FcγR-Induced Glycolytic Reprogramming of Human Macrophages. Newling M, Sritharan L, van der Ham AJ, Hoepel W, Fiechter RH, de Boer L, Zaat SAJ, Bisoendial RJ, Baeten DLP, Everts B, den Dunnen J. J Immunol. 2019 Jul 1;203(1):225-235.
- FcγR-TLR Cross-Talk Enhances TNF Production by Human Monocyte-Derived DCs via IRF5-Dependent Gene Transcription and Glycolytic Reprogramming. Hoepel W, Newling M, Vogelpoel LTC, Sritharan L, Hansen IS, Kapsenberg ML, Baeten DLP, Everts B, den Dunnen J. Front Immunol. 2019 Apr 8;10:739.
- FcγRIII stimulation breaks the tolerance of human nasal epithelial cells to bacteria through cross-talk with TLR4. Golebski K, Hoepel W, van Egmond D, de Groot EJ, Amatngalim GD, Beekman JM, Fokkens WJ, van Drunen CM, den Dunnen J. Mucosal Immunol. 2019 Mar;12(2):425-433.
- FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming. Hansen IS, Krabbendam L, Bernink JH, Loayza-Puch F, Hoepel W, van Burgsteden JA, Kuijper EC, Buskens CJ, Bemelman WA, Zaat SAJ, Agami R, Vidarsson G, van den Brink GR, de Jong EC, Wildenberg ME, Baeten DLP, Everts B, den Dunnen J. Nat Commun. 2018 Feb 28;9(1):863.
- Control of cytokine production by human fc gamma receptors: implications for pathogen defense and autoimmunity. Vogelpoel LT, Baeten DL, de Jong EC, den Dunnen J. Front Immunol. 2015 Feb 24;6:79.
- Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages. Vogelpoel LT, Hansen IS, Rispens T, Muller FJ, van Capel TM, Turina MC, Vos J, Baeten DL, Kapsenberg ML, de Jong EC, den Dunnen J. Nat Commun. 2014 Nov 13;5:5444.
- IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and FcγRIIa in human dendritic cells. den Dunnen J, Vogelpoel LT, Wypych T, Muller FJ, de Boer L, Kuijpers TW, Zaat SA, Kapsenberg ML, de Jong EC. Blood. 2012 Jul 5;120(1):112-21.