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.



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

Complex Regulation of Alarmins S100A8/A9 and Secretion via Gasdermin-D Pores Exacerbates Autoinflammation in Familial Mediterranean Fever

Jorch, 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