Role of S100A8/A9 dimers and tetramers in the regulation of neutrophil dynamics in chronic inflammation
The aim of the present proposal is to understand how neutrophils are controlled to prevent un-wanted immune system activation. We hypothesize that S100A8/A9 with its two occurring quaternary structures dimer versus tetramer differentially modulate neutrophils, with tetramers keeping them in a silent but alert mode upon dimer activation, thereby locally confining neutrophil activity. A better understanding of these regulatory mechanisms and how they can be tuned will pave the way towards novel therapeutic interventions in chronic inflammatory neutrophil-driven diseases.
Team
Publications
The Nuclear Receptor NR4A1 Serves as a Neutrophil-Intrinsic Regulator Mitigating Stroke SeverityStrecker, J.-K.; Schmidt, Y.; Liebmann, M.; Walter, C.; Roth, S.; Aleth, H.; Börsch, A.-L.; Schmidt-Pogoda, A.; Beuker, C.; Yusuf, A. M.; Revenstorff, J.; Osei-Sarpong, C.; Krafft, L.; Schwarze, A.-S.; Heming, M.; Richter, M.; Kuhlmann, T.; Hucke, S.; Heming, J.-N.; Hansen, U.; Hagemann, N.; Bader, A.; Gao, J.; Walzog, B.; Maier-Begandt, D.; Chevre, R.; Hanschmann, E.-M.; Lücke, M.; Sommer, C.; Hermann, D. M.; Roth, J.; Thomas, C.; Meyer Zu Hörste, G.; Gunzer, M.; Vogl, T.; Zarbock, A.; Rosenbauer, F.; Silvestre-Roig, C.; Söhnlein, O.; Klotz, L.; Minnerup, J.
2025 bioRxiv
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RhoA GAP Myo9b Regulates Β2-Integrin Activity and Neutrophil Recruitment during Murine Acute Kidney InjuryCappenberg, A.; Oguama, M.; Richter, M.; Margraf, A.; Amini, W.; Lindental, P.; Mersmann, S.; Bardel, B.; Block, H.; Vogl, T.; Soehnlein, O.; Ley, K.; Rossaint, J.; Zarbock, A.
2025 Blood
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Cytosolic S100A8/A9 Promotes Ca2+ Supply at LFA-1 Adhesion Clusters during Neutrophil RecruitmentNapoli, M.; Immler, R.; Rohwedder, I.; Lupperger, V.; Pfabe, J.; Gonzalez Pisfil, M.; Yevtushenko, A.; Vogl, T.; Roth, J.; Salvermoser, M.; Dietzel, S.; Slak Rupnik, M.; Marr, C.; Walzog, B.; Sperandio, M.; Pruenster, M.
2024 Elife
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Redistribution of PU.1 Partner Transcription Factor RUNX1 Binding Secures Cell Survival during LeukemogenesisBender, A.; Boydere, F.; Jayavelu, A. K.; Tibello, A.; König, T.; Aleth, H.; Meyer Zu Hörste, G.; Vogl, T.; Rosenbauer, F.
2024 EMBO J
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Neonatal neutrophils exhibit reduced NLRP3 inflammasome activationWackerbarth, L. M.; Seifert, S. B.; Napoli, M.; Rohwedder, I.; Vogl, T.; Scheiermann, C.; Kolben, T.; Nussbaum, C.; Pruenster, M.; Immler, R.; Sperandio, M.
2024 J Leukoc Biol
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Functional Multi-Organelle Units Control Inflammatory Lipid Metabolism of MacrophagesZimmermann, J. A.; Lucht, K.; Stecher, M.; Badhan, C.; Glaser, K. M.; Epple, M. W.; Koch, L. R.; Deboutte, W.; Manke, T.; Ebnet, K.; Brinkmann, F.; Fehler, O.; Vogl, T.; Schuster, E.-M.; Bremser, A.; Buescher, J. M.; Rambold, A. S.
2024 Nat Cell Biol
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E-Selectin-Mediated Rapid NLRP3 Inflammasome Activation Regulates S100A8/S100A9 Release from Neutrophils via Transient Gasdermin D Pore Formation.Pruenster, M.; Immler, R.; Roth, J.; Kuchler, T.; Bromberger, T.; Napoli, M.; Nussbaumer, K.; Rohwedder, I.; Wackerbarth, L. M.; 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.
2023 Nat Immunol
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S100A8/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritisvon Wulffen, M.; Luehrmann, V.; Robeck, S.; Russo, A.; Fischer-Riepe, L.; van den Bosch, M.; van Lent, P.; Loser, K.; Gabrilovich, D. I.; Hermann, S.; Roth, J.; Vogl, T.
2023 Cell Reports
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The Roles of Toll-like Receptor 4, CD33, CD68, CD69, or CD147/EMMPRIN for Monocyte Activation by the DAMP S100A8/S100A9Möller, A.; Jauch-Speer, S.-L.; Gandhi, S.; Vogl, T.; Roth, J.; Fehler, O.
2023 Front Immunol
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S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of LeukocytesWolf, M.; Joseph, R.; Austermann, J.; Scharrnbeck-Davis, C.; Hermann, S.; Roth, J.; Vogl, T.
2023 Biomedicines
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Complex Regulation of Alarmins S100A8/A9 and Secretion via Gasdermin-D Pores Exacerbates Autoinflammation in Familial Mediterranean FeverJorch, S. K.; McNally, A.; Berger, P.; Wolf, J.; Kaiser, K.; Chetrusca Covash, A.; Robeck, S.; Pastau, I.; Fehler, O.; Jauch-Speer, S.-L.; Hermann, S.; Schäfers, M.; Van Gorp, H.; Kanneganti, A.; Dehoorne, J.; Haerynck, F.; Penco, F.; Gattorno, M.; Chae, J. J.; Kubes, P.; Lamkanfi, M.; Wullaert, A.; Sperandio, M.; Vogl, T.; Roth, J.; Austermann, J.
2023 J Allergy Clin Immunol
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Role of S100A8/A9 in Platelet–Neutrophil Complex Formation during Acute InflammationRevenstorff, J.; Ludwig, N.; Hilger, A.; Mersmann, S.; Lehmann, M.; Grenzheuser, J. C.; Kardell, M.; Bone, J.; Kötting, N. M.; Marx, N. C.; Roth, J.; Vogl, T.; Rossaint, J.
2022 Cells
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Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on MonocytesRusso, A.; Schürmann, H.; Brandt, M.; Scholz, K.; Matos, A. L. L.; Grill, D.; Revenstorff, J.; Rembrink, M.; von Wulffen, M.; Fischer-Riepe, L.; Hanley, P. J.; Häcker, H.; Prünster, M.; Sánchez-Madrid, F.; Hermann, S.; Klotz, L.; Gerke, V.; Betz, T.; Vogl, T.; Roth, J.
2022 Advanced Science
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