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Stromal cells as primary drivers of immunopathology: towards targeted disease modification in spondyloarthritis

Total Cost €


EC-Contrib. €






 Inflammostrome project word cloud

Explore the words cloud of the Inflammostrome project. It provides you a very rough idea of what is the project "Inflammostrome" about.

bone    primary    diseases    expression    disorders    play    exposed    profile    inflammatory    disease    remodelling    chronic    cellular    experimental    spondyloarthritis    population    ing    alterations    synovial    patients    effect    debilitating    translational    vivo    ex    collectively    validate    activation    myeloid    indicating    models    inflammation    found    animal    unknown    sufficient    il    sampling    experiments    structural    demonstrated    abnormal    drivers    pro    cells    molecular    prevalent    rheumatic    23    drive    act    stressed    upstream    cytokines    unravel    damage    functional    potently    inhibition    vitro    express    spa    tissue    tissues    contain    pathologic    treatments    stromal    unmet    sources    myofibroblasts    remodeling    mechanisms    17    cytokine    failed    immune    blocks    mediated    downstream    dynamic    shown    stress    proven    interventions    pathogenic    human    contribution    induce    therapeutic    drives    tnf   

Project "Inflammostrome" data sheet

The following table provides information about the project.


Organization address
address: MEIBERGDREEF 15
postcode: 1105AZ

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Project website
 Total cost 1˙599˙466 €
 EC max contribution 1˙599˙466 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2018-12-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Pro-inflammatory cytokines play a crucial role in chronic inflammatory diseases. Focusing on spondyloarthritis (SpA), a prevalent and debilitating rheumatic condition characterized by inflammation and abnormal new bone formation, we demonstrated that TNF and IL-23/IL-17 inhibition potently blocks inflammation. However, these treatments have no proven effect on pathologic new bone formation and the resulting structural damage, indicating the unmet need for understanding upstream disease mechanisms. Immune cells, in particular myeloid cells, have been shown to be the major sources of TNF and IL-23 in experimental models. However, we and others failed to demonstrate abnormal cytokine production by myeloid cells in human SpA. What drives these pathogenic cytokines thus remains unknown.

We recently found that SpA synovial tissues contain an abnormal stromal population of myofibroblasts, that these myofibroblasts express TNF and IL-23 in vivo and in vitro when exposed to cellular stress, and that stromal expression of these cytokines does not only drive inflammatory responses in vitro but is required and sufficient to induce experimental SpA in vivo. Therefore, we propose that stressed stromal cells can act as primary drivers of cytokine-mediated tissue inflammation and remodelling. Using a translational approach - dynamic sampling of primary human target tissues, functional experiments ex vivo and in vitro, animal models, and targeted interventions in patients – we aim to unravel the role of stromal cells in SpA by defining: 1) the molecular profile of the stromal alterations, 2) the mechanisms of cytokine production by stromal cells, 3) the activation of downstream inflammatory pathways, 4) the role of stromal alterations in tissue remodeling, and 5) the contribution of stromal pathways to experimental and human SpA. Collectively, this project will allow to validate stromal cells as novel therapeutic targets for SpA and related disorders.


year authors and title journal last update
List of publications.
2018 Francesco Ciccia, Giuliana Guggino, Michael Zeng, Ranjeny Thomas, Vidya Ranganathan, Arifur Rahman, Riccardo Alessandro, Aroldo Rizzo, Laura Saieva, Federica Macaluso, Sergio Peralta, Diana Di Liberto, Francesco Dieli, Paola Cipriani, Roberto Giacomelli, Dominique Baeten, Nigil Haroon
Pro-inflammatory CX3CR1 + CD59 + TL1A + IL-23 + monocytes are expanded in patients with Ankylosing Spondylitis and modulate ILC3 immune functions
published pages: , ISSN: 2326-5191, DOI: 10.1002/art.40582
Arthritis & Rheumatology 2020-01-21
2018 Leonieke J.J. van Mens, Marleen G.H. van de Sande, Dominique L.P. Baeten
New treatment paradigms in spondyloarthritis
published pages: 79-86, ISSN: 1040-8711, DOI: 10.1097/BOR.0000000000000457
Current Opinion in Rheumatology 30/1 2020-01-21
2018 Sophie Glatt, Dominique Baeten, Terry Baker, Meryn Griffiths, Lucian Ionescu, Alastair D G Lawson, Ash Maroof, Ruth Oliver, Serghei Popa, Foteini Strimenopoulou, Pavan Vajjah, Mark I L Watling, Nataliya Yeremenko, Pierre Miossec, Stevan Shaw
Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation
published pages: 523-532, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2017-212127
Annals of the Rheumatic Diseases 77/4 2020-01-21
2018 Man Wai Tang, Beatriz Malvar Fernández, Simon P Newsom, Jaap D van Buul, Timothy R D J Radstake, Dominique L Baeten, Paul P Tak, Kris A Reedquist, Samuel García
Class 3 semaphorins modulate the invasive capacity of rheumatoid arthritis fibroblast-like synoviocytes
published pages: 909-920, ISSN: 1462-0324, DOI: 10.1093/rheumatology/kex511
Rheumatology 57/5 2020-01-21
2017 Melissa N. van Tok, Nimman Satumtira, Martha Dorris, Desirée Pots, Gleb Slobodin, Marleen G. van de Sande, Joel D. Taurog, Dominique L. Baeten, Leonie M. van Duivenvoorde
Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2017.00920
Frontiers in Immunology 8 2020-01-21
2017 Leonieke J J van Mens, Maureen C Turina, Marleen G H van de Sande, Mike T Nurmohamed, Arno W R van Kuijk, Dominique L P Baeten
Residual disease activity in psoriatic arthritis: discordance between the rheumatologist’s opinion and minimal disease activity measurement
published pages: 283-290, ISSN: 1462-0324, DOI: 10.1093/rheumatology/kex183
Rheumatology 57/2 2020-01-21
2016 Maureen C. Turina, Janneke J. de Winter, Jacky E. Paramarta, Mihaela Gamala, Nataliya Yeremenko, Marita N. Nabibux, Robert Landewé, Dominique L. Baeten
Clinical and Imaging Signs of Spondyloarthritis in First-Degree Relatives of HLA-B27-Positive Ankylosing Spondylitis Patients: The Pre-Spondyloarthritis (Pre-SpA) Cohort Study
published pages: 2444-2455, ISSN: 2326-5191, DOI: 10.1002/art.39766
Arthritis & Rheumatology 68/10 2020-01-21
2016 Oliwia Rysnik, Kirsty McHugh, Leonie van Duivenvoorde, Melissa van Tok, Joel Taurog, Simon Kollnberger, Dominique Baeten, Paul Bowness
Data showing non-conventional HLA-B27 expression in axial joints and gut tissue from B27 transgenic rats, and in frozen and paraffin-fixed synovial SpA tissue
published pages: 100-111, ISSN: 2352-3409, DOI: 10.1016/j.dib.2016.08.046
Data in Brief 9 2020-01-21
2016 Chiara Angiolilli, Pawel A Kabala, Aleksander M Grabiec, Iris M Van Baarsen, Bradley S Ferguson, Samuel García, Beatriz Malvar Fernandez, Timothy A McKinsey, Paul P Tak, Gianluca Fossati, Paolo Mascagni, Dominique L Baeten, Kris A Reedquist
Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes
published pages: 277-285, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2015-209064
Annals of the Rheumatic Diseases 76/1 2020-01-21
2018 Janneke de Winter, Manouk de Hooge, Marleen van de Sande, Henriëtte de Jong, Lonneke van Hoeven, Anoek de Koning, Inger Jorid Berg, Roberta Ramonda, Dominique Baeten, Désirée van der Heijde, Angelique Weel, Robert Landewé
Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain
published pages: 1042-1048, ISSN: 2326-5191, DOI: 10.1002/art.40475
Arthritis & Rheumatology 70/7 2020-01-21
2018 Yasunori Omata, Michael Frech, Tatjana Primbs, Sébastien Lucas, Darja Andreev, Carina Scholtysek, Kerstin Sarter, Markus Kindermann, Nataliya Yeremenko, Dominique L. Baeten, Nico Andreas, Thomas Kamradt, Aline Bozec, Andreas Ramming, Gerhard Krönke, Stefan Wirtz, Georg Schett, Mario M. Zaiss
Group 2 Innate Lymphoid Cells Attenuate Inflammatory Arthritis and Protect from Bone Destruction in Mice
published pages: 169-180, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.06.005
Cell Reports 24/1 2020-01-21
2017 Jürgen Braun, Xenofon Baraliakos, Atul Deodhar, Dominique Baeten, Joachim Sieper, Paul Emery, Aimee Readie, Ruvie Martin, Shephard Mpofu, Hanno B Richards
Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study
published pages: 1070-1077, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2016-209730
Annals of the Rheumatic Diseases 76/6 2020-01-21
2016 Jacqueline E. Paramarta, Maureen C. Turina, Troy Noordenbos, Tanja F. Heijda, Iris C. Blijdorp, Nataliya Yeremenko, Dominique Baeten
A proof-of-concept study with the tyrosine kinase inhibitor nilotinib in spondyloarthritis
published pages: , ISSN: 1479-5876, DOI: 10.1186/s12967-016-1050-2
Journal of Translational Medicine 14/1 2020-01-21
2018 Janneke J. de Winter, Marleen G. van de Sande, Niklas Baerlecken, Inger Berg, Roberta Ramonda, Désirée van der Heijde, Floris A. van Gaalen, Torsten Witte, Dominique L. Baeten
Anti-CD74 antibodies have no diagnostic value in early axial spondyloarthritis: data from the spondyloarthritis caught early (SPACE) cohort
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-018-1535-x
Arthritis Research & Therapy 20/1 2020-01-21
2017 Stephanie van den Brandt, Astrid Zbinden, Dominique Baeten, Peter M. Villiger, Monika Østensen, Frauke Förger
Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-017-1269-1
Arthritis Research & Therapy 19/1 2020-01-21
2016 Atul A. Deodhar, Maxime Dougados, Dominique L. Baeten, James Cheng-Chung Wei, Piet Geusens, Aimee Readie, Hanno B. Richards, Ruvie Martin, Brian Porter
Effect of Secukinumab on Patient-Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized Trial (MEASURE 1)
published pages: 2901-2910, ISSN: 2326-5191, DOI: 10.1002/art.39805
Arthritis & Rheumatology 68/12 2020-01-21
2017 Maria J. Levels, Melissa N. Van Tok, Tineke Cantaert, Juan D. Cañete, Frans G. M. Kroese, Kristine Germar, Hergen Spits, Dominique L. P. Baeten, Nataliya G. Yeremenko
The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation
published pages: 750-762, ISSN: 2326-5191, DOI: 10.1002/art.39993
Arthritis & Rheumatology 69/4 2020-01-21
2018 Filip Van den Bosch, Philip J Mease, Joachim Sieper, Dominique L Baeten, Yinglin Xia, Su Chen, Aileen L Pangan, In-Ho Song
Long-term efficacy and predictors of remission following adalimumab treatment in peripheral spondyloarthritis: 3-year results from ABILITY-2
published pages: e000566, ISSN: 2056-5933, DOI: 10.1136/rmdopen-2017-000566
RMD Open 4/1 2020-01-21
2016 Melissa N. van Tok, Nataliya G. Yeremenko, Christine A. Teitsma, Barbara E. Kream, Véronique L. Knaup, Rik J. Lories, Dominique L. Baeten, Leonie M. van Duivenvoorde
Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis
published pages: e0163632, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0163632
PLOS ONE 11/10 2020-01-21
2017 James C.-C. Wei, Dominique Baeten, Joachim Sieper, Atul Deodhar, Vaishali Bhosekar, Ruvie Martin, Brian Porter
Efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis: 52-week pooled results from two phase 3 studies
published pages: 589-596, ISSN: 1756-1841, DOI: 10.1111/1756-185X.13094
International Journal of Rheumatic Diseases 20/5 2020-01-21
2017 Maureen C Turina, Nataliya Yeremenko, Floris van Gaalen, Maikel van Oosterhout, Inger J Berg, Ramona Ramonda, Cristina (M C) Lebre, Robert Landewé, Dominique Baeten
Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort
published pages: e000319, ISSN: 2056-5933, DOI: 10.1136/rmdopen-2016-000319
RMD Open 3/1 2020-01-21
2017 Chiara Angiolilli, Dominique L Baeten, Timothy R Radstake, Kris A Reedquist
The acetyl code in rheumatoid arthritis and other rheumatic diseases
published pages: 447-461, ISSN: 1750-1911, DOI: 10.2217/epi-2016-0136
Epigenomics 9/4 2020-01-21
2016 Sophie J. Bernelot Moens, Sander I. van Leuven, Kang H. Zheng, Stefan R. Havik, Miranda V. Versloot, Leonie M. van Duivenvoorde, Michael Hahne, Erik S. G. Stroes, Dominique L. Baeten, Anouk A. J. Hamers
Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques
published pages: e0164690, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0164690
PLOS ONE 11/11 2020-01-21
2017 Ivo S. Hansen, Willianne Hoepel, Sebastiaan A. J. Zaat, Dominique L. P. Baeten, Jeroen den Dunnen
Serum IgA Immune Complexes Promote Proinflammatory Cytokine Production by Human Macrophages, Monocytes, and Kupffer Cells through FcαRI–TLR Cross-Talk
published pages: 4124-4131, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1700883
The Journal of Immunology 199/12 2020-01-21
2017 Pawel A. Kabala, Chiara Angiolilli, Nataliya Yeremenko, Aleksander M. Grabiec, Barbara Giovannone, Desiree Pots, Timothy R. Radstake, Dominique Baeten, Kris A. Reedquist
Endoplasmic reticulum stress cooperates with Toll-like receptor ligation in driving activation of rheumatoid arthritis fibroblast-like synoviocytes
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-017-1386-x
Arthritis Research & Therapy 19/1 2020-01-21
2016 Janneke J. de Winter, Leonieke J. van Mens, Désirée van der Heijde, Robert Landewé, Dominique L. Baeten
Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-016-1093-z
Arthritis Research & Therapy 18/1 2020-01-21
2016 Taco W. Kuijpers, Sanne Vendelbosch, Merlijn van den Berg, Dominique L.P. Baeten
Killer immunoglobulin receptor genes in spondyloarthritis
published pages: 368-375, ISSN: 1040-8711, DOI: 10.1097/BOR.0000000000000302
Current Opinion in Rheumatology 28/4 2020-01-21
2016 Francesco Ciccia, Giuliana Guggino, Angelo Ferrante, Stefania Raimondo, Rodolfo Bignone, Vito Rodolico, Sergio Peralta, Melissa Van Tok, Alessandra Cannizzaro, Claudia Schinocca, Piero Ruscitti, Paola Cipriani, Roberto Giacomelli, Riccardo Alessandro, Francesco Dieli, Aroldo Rizzo, Dominique Baeten, Giovanni Triolo
Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis
published pages: 1922-1931, ISSN: 2326-5191, DOI: 10.1002/art.39649
Arthritis & Rheumatology 68/8 2020-01-21
2018 Ivo S. Hansen, Lisette Krabbendam, Jochem H. Bernink, Fabricio Loayza-Puch, Willianne Hoepel, Johan A. van Burgsteden, Elsa C. Kuijper, Christianne J. Buskens, Willem A. Bemelman, Sebastiaan A. J. Zaat, Reuven Agami, Gestur Vidarsson, Gijs R. van den Brink, Esther C. de Jong, Manon E. Wildenberg, Dominique L. P. Baeten, Bart Everts, Jeroen den Dunnen
FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03318-5
Nature Communications 9/1 2020-01-21
2016 Fleur M van der Valk, Sophie J Bernelot Moens, Simone L Verweij, Aart C Strang, Aart J Nederveen, Hein J Verberne, Michael T Nurmohamed, Dominique L Baeten, Erik S G Stroes
Increased arterial wall inflammation in patients with ankylosing spondylitis is reduced by statin therapy
published pages: 1848-1851, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2016-209176
Annals of the Rheumatic Diseases 75/10 2020-01-21
2018 Lianne J. N. Kraal, Marieke L. Nijland, Kristine L. Germar, Dominique L. P. Baeten, Ineke J. M. ten Berge, Cynthia M. Fehres
Anti-citrullinated protein antibody response after primary EBV infection in kidney transplant patients
published pages: e0197219, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0197219
PLOS ONE 13/5 2020-01-21
2018 Stefan T G Bruijnen, Nicki J F Verweij, Leonie M van Duivenvoorde, Nathalie Bravenboer, Dominique L P Baeten, Christiaan J van Denderen, Irene E van der Horst-Bruinsma, Alexandre E Voskuyl, Martijn Custers, Peter M van de Ven, Joost C J Bot, Bouke J H Boden, Adriaan A Lammertsma, Otto S H Hoekstra, Pieter G H M Raijmakers, Conny J van der Laken
Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography
published pages: 631-638, ISSN: 1462-0324, DOI: 10.1093/rheumatology/kex448
Rheumatology 57/4 2020-01-21
2017 Leonieke J. J. van Mens, Marleen G. H. van de Sande, Inka A. Fluri, Sadaf Atiqi, Arno W. R. van Kuijk, Dominique L. P. Baeten
Residual disease activity and treatment adjustments in psoriatic arthritis in current clinical practice
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-017-1424-8
Arthritis Research & Therapy 19/1 2020-01-21
2018 Katy A. Lloyd, Johanna Steen, Khaled Amara, Philip J. Titcombe, Lena Israelsson, Susanna L. Lundström, Diana Zhou, Roman A. Zubarev, Evan Reed, Luca Piccoli, Cem Gabay, Antonio Lanzavecchia, Dominique Baeten, Karin Lundberg, Daniel L. Mueller, Lars Klareskog, Vivianne Malmström, Caroline Grönwall
Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: Implications for B-cell selection
published pages: 1030-1045, ISSN: 0014-2980, DOI: 10.1002/eji.201747446
European Journal of Immunology 48/6 2020-01-21
2018 Leonieke J. J. van Mens, Marleen G.H van de Sande, Silvia Menegatti, Sija Chen, Iris C. J. Blijdorp, Henriette M. de Jong, Inka A. Fluri, Talia E. Latuhihin, Arno W. R. van Kuijk, Lars Rogge, Nataliya G. Yeremenko, Dominique L. P. Baeten
IL-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses
published pages: , ISSN: 2326-5191, DOI: 10.1002/art.40581
Arthritis & Rheumatology 2020-01-21
2016 Troy Noordenbos, Iris Blijdorp, Sijia Chen, Jan Stap, Erik Mul, Juan D. Cañete, Erik Lubberts, Nataliya Yeremenko, Dominique Baeten
Human mast cells capture, store, and release bioactive, exogenous IL-17A
published pages: 453-462, ISSN: 0741-5400, DOI: 10.1189/jlb.3HI1215-542R
Journal of Leukocyte Biology 100/3 2020-01-21
2016 Charlotte Hua, Rachel Audo, Nataliya Yeremenko, Dominique Baeten, Michael Hahne, Bernard Combe, Jacques Morel, Claire Daïen
A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells
published pages: 64-72, ISSN: 0896-8411, DOI: 10.1016/j.jaut.2016.06.002
Journal of Autoimmunity 73 2020-01-21
2018 Leonieke J J van Mens, Marleen G H van de Sande, Arno W R van Kuijk, Dominique Baeten, Laura C Coates
Ideal target for psoriatic arthritis? Comparison of remission and low disease activity states in a real-life cohort
published pages: 251-257, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2017-211998
Annals of the Rheumatic Diseases 77/2 2020-01-21

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