Targeting cell-intrinsic mechanisms of neutrophil functions

The response of neutrophils to microbial challenges involves both intracellular and extracellular immune pathways. The translation of external signals into appropriate transcriptional immune response programs is highly dependent on transcription factors. We have recently shown that the transcription factor PU.1 not only controls the transcription of immune genes, but also ensures immune defence by promoting the proteasomal degradation of the pre-synthesized immune proteome. Hence, our results have revealed a novel, pathogen- dependent, transcription-driven yet post-translationally controlled immune response network that offers new perspectives for neutrophil immunomodulation. We will build on these findings to interfere with cell-intrinsic control programs of neutrophil immune functions by targeting both the transcriptional and post-transcriptional axes. Our goal is to identify epigenetic and proteasomal pathways that are central to the immune activities of neutrophils and, as such, could be effective targets in immunotherapeutic settings. In addition, we investigate a novel mechanism by which the proteasome could induce immune status-dependent epigenomic remodelling via controlling the stabilization of the transcription factor ETS2 protein.

Rosenbauer
Frank, PhD

UniMS

Institute of Molecular Tumour Biology

Team

Aleth
Hanna, PhD

UniMS

Publications

A1 A2 A3 A5 B3 B4 C5 Z1 Divergent Granulopoiesis at Extramedullary Sites Safeguards Antibacterial Host Defense Silvestre-Roig, C.; Chevre, R.; Farjia, M.; Bender, A.; Vöcking, L. M.; Richter, M.; Hageb, A.; Suerdieck, V.; Arenas Cerro, F. J.; Braster, Q.; Guzman, M.; Sintes, J.; Sharma, S.; Lemnitzer, P.; Tulotta, C.; Börgeling, Y.; Herrero-Cervera, A.; Flueter, H.; Reinartz Groba, S. N.; Ahern, D.; Osei-Sarpong, C.; Zimmer, R.; Alonso-Gonzalez, N.; Ortega, E.; Lienenklaus, S.; Kalinke, U.; Ludwig, S.; Engel, D. R.; Rosenbauer, F.; Monaco, C.; Dersch, P.; Kibler, A.; Cerutti, A.; Chavakis, T.; Benedito, R.; Hidalgo, A.; Jablonska, J.; Palomino-Segura, M.; Soehnlein, O. 2026 Sci Immunol https://doi.org/10.1126/sciimmunol.adw7077
A1 A2 B2 B3 C1 C3 C6 C7 E Z1 The Nuclear Receptor NR4A1 Serves as a Neutrophil-Intrinsic Regulator Mitigating Stroke Severity Strecker, 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 https://doi.org/10.1101/2025.09.19.677282
A1 A2 B2 B3 C1 C6 INF Neutrophil Progenitor Mobilization Is a Distinct Feature of STEMI and Predicts Survival Richter, M.; Von Göwels, J.; Fähndrich, M.; Fernandez, C. L.; Grohn, K.; Schwarz, D.; Lang, A.; Polzin, A.; Farinola, L.; Gosh, S.; Groba, S. R.; Heming, J.-N.; Aleth, H.; Rübsamen, N.; Radecke, T.; Rosenbauer, F.; Sickmann, A.; Karch, A.; Zarbock, A.; Minnerup, J.; Sindermann, J.; Bender, A.; Rossaint, J.; Ormanns, S.; Gunzer, M.; Reinecke, H.; Makowski, L.; Jung, C.; Silvestre-Roig, C.; Kelm, M.; Gerdes, N.; Chevre, R.; Lange, S.; Soehnlein, O. 2025 Research Square https://doi.org/10.21203/rs.3.rs-6474581/v2
B3 C7 E Redistribution of PU.1 Partner Transcription Factor RUNX1 Binding Secures Cell Survival during Leukemogenesis Bender, A.; Boydere, F.; Jayavelu, A. K.; Tibello, A.; König, T.; Aleth, H.; Meyer Zu Hörste, G.; Vogl, T.; Rosenbauer, F. 2024 EMBO J https://doi.org/10.1038/s44318-024-00295-y
A2 A3 A4 A5 A6 E A7 B1 B2 B3 B5 E C1 C2 C3 C5 AP1 Neutrophils - Biology and Diversity Maier-Begandt, D.; Alonso-Gonzalez, N.; Klotz, L.; Erpenbeck, L.; Jablonska, J.; Immler, R.; Hasenberg, A.; Mueller, T. T.; Herrero-Cervera, A.; Aranda-Pardos, I.; Flora, K.; Zarbock, A.; Brandau, S.; Schulz, C.; Soehnlein, O.; Steiger, S.; the TRR332 consortium. 2023 Nephrol Dial Transplant https://doi.org/10.1093/ndt/gfad266