Imaging of inflammatory and regulatory mechanisms in arthritis

Principal investigators: Sven Hermann, Thomas Vogl
Project number: CRC 1450 C03
Project term: 01/2021–12/2024

Graphical abstract
© CRC inSight

Immune-regulatory mechanisms limiting immunological responses are promising new therapeutic targets in chronic autoinflammatory diseases (1). This project will investigate to what extent the alarmin S100A8/A9 reprograms myeloid cells to a regulatory phenotype in a negative feedback loop, in particular immunosuppressive MDSCs, and thereby dampens down the immune response in arthritis (2).

Multiscale imaging methods will be used to localize and study the interaction of MDSCs, S100A8/A9 and activated leukocytes in mouse models of acute and chronic arthritis over time (3, 4) and to evaluate the therapeutic potential of MDSCs, either induced in vivo or after adoptive cell transfer of in vitro expanded MDSCs (5).


Principal investigators


The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.


Honold L, Austrup M, Faust A, Konken CP, Schwegmann K, Zinnhardt B, Daniliuc CG, Haufe G, Schafers M, Kopka K, Hermann S. Towards Optimized Bioavailability of (99m)Tc-Labeled Barbiturates for Non-invasive Imaging of Matrix Metalloproteinase Activity. Mol Imaging Biol 2022;24: 434-443. Abstract
Schwarz C, Buchholz R, Jawad M, Hoesker V, Terwesten-Sole C, Karst U, Linsen L, Vogl T, Hoerr V, Wildgruber M, Faber C. Fingerprints of Element Concentrations in Infective Endocarditis Obtained by Mass Spectrometric Imaging and t-Distributed Stochastic Neighbor Embedding. ACS Infect Dis 2022Abstract


Depke DA, Konken CP, Rosner L, Hermann S, Schafers M, Rentmeister A. A novel (18)F-labeled clickable substrate for targeted imaging of SNAP-tag expressing cells by PET in vivo. Chem Commun (Camb) 2021;57: 9850-9853. Abstract


Roll W, Markwardt NA, Masthoff M, Helfen A, Claussen J, Eisenblatter M, Hasenbach A, Hermann S, Karlas A, Wildgruber M, Ntziachristos V, Schafers M. Multispectral Optoacoustic Tomography of Benign and Malignant Thyroid Disorders: A Pilot Study. J Nucl Med 2019;60: 1461-1466. Abstract


Gran S, Honold L, Fehler O, Zenker S, Eligehausen S, Kuhlmann MT, Geven E, den Bosch M van, van Lent P, Spiekermann C, Hermann S, Vogl T, Schäfers M, Roth J. Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment_in vivo_. Theranostics 2018;8: 2407-2423. Abstract
Voeller T, Faust A, Roth J, Schafers M, Vogl T, Hermann S. A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity In Vivo. Mol Imaging Biol 2018;20: 407-416. Abstract
Vogl T, Stratis A, Wixler V, Voller T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty D, Frohling M, Paruzel P, Wehmeyer C, Hermann S, Papantonopoulou O, Geyer C, Loser K, Schafers M, Ludwig S, Stoll M, Leanderson T, Schultze JL, Konig S, Pap T, Roth J. Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation. J Clin Invest 2018;128: 1852-1866. Abstract


Geven EJW, van den Bosch MHJ, Di Ceglie I, Ascone G, Abdollahi-Roodsaz S, Sloetjes AW, Hermann S, Schafers M, van de Loo FAJ, van der Kraan PM, Koenders MI, Foell D, Roth J, Vogl T, van Lent PLEM. S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis. Arthritis Res Ther 2016;18: 247. Abstract
Pruenster M, Vogl T, Roth J, Sperandio M. S100A8/A9: From basic science to clinical application. Pharmacol Ther 2016;167: 120-131. Abstract


Faust A, Voller T, Busch F, Schafers M, Roth J, Hermann S, Vogl T. Development and evaluation of a non-peptidic ligand for the molecular imaging of inflammatory processes using S100A9 (MRP14) as a novel target. Chem Commun (Camb) 2015;51: 15637-15640. Abstract


Vogl T, Eisenblatter M, Voller T, Zenker S, Hermann S, van Lent P, Faust A, Geyer C, Petersen B, Roebrock K, Schafers M, Bremer C, Roth J. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 2014;5: 4593. Abstract


Petersen B, Wolf M, Austermann J, van Lent P, Föll D, Ahlmann M, Kupas V, Loser K, Sorg C, Roth J, Vogl T. The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis. EMBO J 2013;32: 100-111. Abstract


van Lent PLEM, Grevers L, Blom AB, Sloetjes A, Mort JS, Vogl T, Nacken W, van den Berg WB, Roth J. Myeloid-related proteins S100A8/S100A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritis. Ann Rheum Dis 2008;67: 1750-1758. Abstract