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).
| Hoffmann E, Schache D, Holtke C, Soltwisch J, Niland S, Krahling T, Bergander K, Grewer M, Geyer C, Groeneweg L, Eble JA, Vogl T, Roth J, Heindel W, Maus B, Helfen A, Faber C, Wildgruber M, Gerwing M, Hoerr V. Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy. J Transl Med 2023;21: 577. Abstract
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| Jorch SK, McNally A, Berger P, Wolf J, Kaiser K, Chetrusca Covash A, Robeck S, Pastau I, Fehler O, Jauch-Speer S-L, Hermann S, Schafers M, Van Gorp H, Kanneganti A, Dehoorne J, Haerynck F, Penco F, Gattorno M, Chae JJ, Kubes P, Lamkanfi M, Wullaert A, Sperandio M, Vogl T, Roth J, Austermann J. Complex regulation of alarmins S100A8/A9 and secretion via Gasdermin-D pores exacerbates autoinflammation in Familial Mediterranean Fever. J Allergy Clin Immunol 2023Abstract
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| Pruenster M, Immler R, Roth J, Kuchler T, Bromberger T, Napoli M, Nussbaumer K, Rohwedder I, Wackerbarth LM, Piantoni C, Hennis K, Fink D, Kallabis S, Schroll T, Masgrau-Alsina S, Budke A, Liu W, Vestweber D, Wahl-Schott C, Roth J, Meissner F, Moser M, Vogl T, Hornung V, Broz P, Sperandio M. E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation. Nat Immunol 2023;24: 2021-2031. Abstract
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| Song J, Deshpande T, Zhang X, Hannocks M-J, Lycke N, Cardell SL, Sorokin L. The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation. iScience 2023;26: 106753. Abstract
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| von Wulffen M, Luehrmann V, Robeck S, Russo A, Fischer-Riepe L, van den Bosch M, van Lent P, Loser K, Gabrilovich DI, Hermann S, Roth J, Vogl T. S100A8/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritis. Cell Rep 2023;42: 113006. Abstract
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| Wolf M, Joseph R, Austermann J, Scharrnbeck-Davis C, Hermann S, Roth J, Vogl T. S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes. Biomedicines 2023;11Abstract |
| Foray C, Barca C, Winkeler A, Wagner S, Hermann S, Schafers M, Grauer OM, Zinnhardt B, Jacobs AH. Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI. J Nucl Med 2022;63: 1386-1393. Abstract
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| Helfen A, Riess J, Fehler O, Stolting M, An Z, Kocman V, Schnepel A, Geyer C, Gerwing M, Masthoff M, Vogl T, Holtke C, Roth J, Ng T, Wildgruber M, Eisenblatter M. In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker. Neoplasia 2022;28: 100792. Abstract
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| 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
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| Rosner L, Konken CP, Depke DA, Rentmeister A, Schafers M. Covalent labeling of immune cells. Curr Opin Chem Biol 2022;68: 102144. Abstract
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| Russo A, Schurmann H, Brandt M, Scholz K, Matos ALL, Grill D, Revenstorff J, Rembrink M, von Wulffen M, Fischer-Riepe L, Hanley PJ, Hacker H, Prunster M, Sanchez-Madrid F, Hermann S, Klotz L, Gerke V, Betz T, Vogl T, Roth J. Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes. Adv Sci (Weinh) 2022: e2201505. Abstract |
| Barca C, Foray C, Hermann S, Herrlinger U, Remory I, Laoui D, Schafers M, Grauer OM, Zinnhardt B, Jacobs AH. The Colony Stimulating Factor-1 Receptor (CSF-1R)-Mediated Regulation of Microglia/Macrophages as a Target for Neurological Disorders (Glioma, Stroke). Front Immunol 2021;12: 787307. Abstract
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| 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
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| Foray C, Valtorta S, Barca C, Winkeler A, Roll W, Müther M, Wagner S, Gardner ML, Hermann S, Schäfers M, Grauer OM, Moresco RM, Zinnhardt B, Jacobs AH. Imaging temozolomide-induced changes in the myeloid glioma microenvironment. Theranostics 2021;11: 2020-2033. Abstract |
| Perego M, Tyurin VA, Tyurina YY, Yellets J, Nacarelli T, Lin C, Nefedova Y, Kossenkov A, Liu Q, Sreedhar S, Pass H, Roth J, Vogl T, Feldser D, Zhang R, Kagan VE, Gabrilovich DI. Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils. Sci Transl Med 2020;12Abstract
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| Zinnhardt B, Muther M, Roll W, Backhaus P, Jeibmann A, Foray C, Barca C, Doring C, Tavitian B, Dolle F, Weckesser M, Winkeler A, Hermann S, Wagner S, Wiendl H, Stummer W, Jacobs AH, Schafers M, Grauer OM. TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma. Neuro Oncol 2020;22: 1030-1043. 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
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| 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 |
