We are a systems immunology laboratory in the Department of Internal Medicine 3 – Rheumatology and Immunology at Erlangen University Hospital.
Our group investigates the mechanisms driving immune cell heterogeneity in tissues and inflammatory conditions and the links to disease variation across individuals. Our approach is characterized by a combination of high dimensional discovery in patient samples (in particular in the context of innovative therapies such as CAR-T cells) with in vitro systems, CRISPR-mediated genetic perturbations and murine models. We also develop novel analysis tools for high dimensional data.
In published work, we demonstrated that neutrophils in homeostasis are organized a chronologically ordered main sequence, termed neutrotime. In experimental inflammation, neutrophils reach distinct polarization states driven by timepoint, tissue and stimulus.
To apply this principle to human immune-mediated disease, we developed a method to jointly analyze murine and human transcriptomic data. Thereby, we identified a transcriptional program which characterizes neutrophils in the arthritic joint in both mice and humans. Functionally, this program was highly enriched for interferon gamma response genes, which we validated on the protein level and using in vitro models.
Recent publications
2024
Bucci, L., Hagen, M., Rothe, T., Raimondo, M.G., Fagni, F., Tur, C.,... Grieshaber Bouyer, R. (2024). Bispecific T cell engager therapy for refractory rheumatoid arthritis . Nature Medicine , 30 (6), 1593-1601. https://doi.org/10.1038/s41591-024-02964-1
Hagen, M., Wirsching, A., Bohr, D., Taubmann, J., Müller, F., Mackensen, A.,... Schett, G. (2024). CAR-T-Zell-Therapie in der Rheumatologie – Was wissen wir bisher? Zeitschrift für Rheumatologie . https://doi.org/10.1007/s00393-024-01514-x
Taubmann, J., Müller, F., Mutlu, M.Y., Völkl, S., Aigner, M., Bozec, A.,... Schett, G. (2024). CD19 Chimeric Antigen Receptor T Cell Treatment: Unraveling the Role of B Cells in Systemic Lupus Erythematosus. Arthritis and Rheumatology , 76 (4), 497-504. https://doi.org/10.1002/art.42784
Wilhelm, A., Chambers, D., Müller, F., Bozec, A., Grieshaber Bouyer, R., Winkler, T.,... Krönke, G. (2024). Selective CAR T cell–mediated B cell depletion suppresses IFN signature in SLE . JCI Insight , 9 (12). https://doi.org/10.1172/jci.insight.179433
2023
Hackert, N.S., Radtke, F.A., Exner, T., Lorenz, H.M., Müller-Tidow, C., Nigrovic, P.A.,... Grieshaber-Bouyer, R. (2023). Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts . Nature Communications , 14 (1). https://doi.org/10.1038/s41467-023-43573-9
2022
Grieshaber-Bouyer, R., Exner, T., Hackert, N.S., Radtke, F.A., Jelinsky, S.A., Halyabar, O.,... Nigrovic, P.A. (2022). Ageing and interferon gamma response drive the phenotype of neutrophils in the inflamed joint . Annals of the Rheumatic Diseases , 81 (6), 805-814. https://doi.org/10.1136/annrheumdis-2021-221866
Huang, F.Y., Cunin, P., Radtke, F.A., Darbousset, R., Grieshaber-Bouyer, R., & Nigrovic, P.A. (2022). Neutrophil transit time and localization within the megakaryocyte define morphologically distinct forms of emperipolesis . Blood Advances , 6 (7), 2081-2091. https://doi.org/10.1182/bloodadvances.2021005097
Neuenfeldt, F., Schumacher, J.C., Grieshaber-Bouyer, R., Habicht, J., Schröder-Braunstein, J., Gauss, A.,... Wabnitz, G. (2022). Inflammation induces pro-NETotic neutrophils via TNFR2 signaling . Cell Reports , 39 (3). https://doi.org/10.1016/j.celrep.2022.110710
Zhao, S., Grieshaber-Bouyer, R., Rao, D.A., Kolb, P., Chen, H., Andreeva, I.,... Merkt, W. (2022). Effect of JAK Inhibition on the Induction of Proinflammatory HLA–DR+CD90+ Rheumatoid Arthritis Synovial Fibroblasts by Interferon-γ . Arthritis and Rheumatology , 74 (3), 441-452. https://doi.org/10.1002/art.41958
2021
Chang, M.H., Levescot, A., Nelson-Maney, N., Blaustein, R.B., Winden, K.D., Morris, A.,... Nigrovic, P.A. (2021). Arthritis flares mediated by tissue-resident memory T cells in the joint . Cell Reports , 37 (4). https://doi.org/10.1016/j.celrep.2021.109902
Grieshaber-Bouyer, R., Radtke, F.A., Cunin, P., Stifano, G., Levescot, A., Nelson-Maney, N.,... Yoshida, H. (2021). The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments . Nature Communications , 12 (1). https://doi.org/10.1038/s41467-021-22973-9
Kiner, E., Willie, E., Schmutz, H., Chandler, J., Schnell, A., Thakore, P.I.,... Yoshida, H. (2021). Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes . Nature Immunology , 22 (2), 216-228. https://doi.org/10.1038/s41590-020-00836-7
Kiner, E., Willie, E., Schmutz, H., Chandler, J., Schnell, A., Thakore, P.I.,... Yoshida, H. (2021). Publisher Correction: Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes (Nature Immunology, (2021), 22, 2, (216-228), 10.1038/s41590-020-00836-7) . Nature Immunology , 22 (5), 666-668. https://doi.org/10.1038/s41590-021-00916-2
Levescot, A., Chang, M.H., Schnell, J., Nelson-Maney, N., Yan, J., Martínez-Bonet, M.,... Nigrovic, P.A. (2021). IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis . Journal of Clinical Investigation , 131 (18). https://doi.org/10.1172/JCI141008
Rose, S.A., Wroblewska, A., Dhainaut, M., Yoshida, H., Shaffer, J.M., Bektesevic, A.,... Yim, A. (2021). A microRNA expression and regulatory element activity atlas of the mouse immune system . Nature Immunology , 22 (7), 914-927. https://doi.org/10.1038/s41590-021-00944-y
2020
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We are a systems immunology laboratory in the Department of Internal Medicine 3 – Rheumatology and Immunology at Erlangen University Hospital.
Our group investigates the mechanisms driving immune cell heterogeneity in tissues and inflammatory conditions and the links to disease variation across individuals. Our approach is characterized by a combination of high dimensional discovery in patient samples (in particular in the context of innovative therapies such as CAR-T cells) with in vitro systems, CRISPR-mediated genetic perturbations and murine models. We also develop novel analysis tools for high dimensional data.
In published work, we demonstrated that neutrophils in homeostasis are organized a chronologically ordered main sequence, termed neutrotime. In experimental inflammation, neutrophils reach distinct polarization states driven by timepoint, tissue and stimulus.
To apply this principle to human immune-mediated disease, we developed a method to jointly analyze murine and human transcriptomic data. Thereby, we identified a transcriptional program which characterizes neutrophils in the arthritic joint in both mice and humans. Functionally, this program was highly enriched for interferon gamma response genes, which we validated on the protein level and using in vitro models.
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2024
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2020
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