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How do immune cells adapt to oxygen and nutrient deficiencies in inflamed tissue?

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Selected Publications
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Glucocorticoids and Bioenergetics

Acute and chronic inflammation can lead to a pronounced lack of oxygen and nutrients in the area of inflammation. How does the immune system manage to remain active despite this?

In acute inflammatory processes such as in the initial phase of bone healing -the fracture hematoma -, but also in chronic inflammation, such as rheumatoid arthritis, cells sometimes need more nutrients and oxygen than the body provides. This can lead to a pronounced lack of these vital substances at the site of inflammation.

In order to be able to continue to functioning, especially immune cells which accumulate in the area of inflammation or in a fracture hematoma have a number of adaptation mechanisms. In this way, they manage to compensate their bioenergetic balance, which is decisive for the survival, development and functional efficiency of all cellular systems.

Our research group is investigating such mechanisms, as they undoubtedly play a central role not only in acute and chronic inflammation, but also in tissue regeneration. Furthermore, these adaptation mechanisms also offer possible starting points for new therapeutic strategies, as well as explanatory approaches for the modes of action of already approved anti-inflammatory drugs such as glucocorticoids.

The adaptation mechanisms of immune cells to an altered microenvironment in inflammatory events differ from species to species. In particular, disease processes in inflammatory joint diseases in humans and regeneration processes in bone healing cannot yet be adequately modelled in animals, making it difficult to transfer the results of these experiments to humans.

Therefore, we are establishing in vitro models based on human cells in order to mimic acute and chronic inflammation such as found in the initial phase of fracture healing and in the inflamed joint. To this end, we are generating a variety of different in vitro 3D disease models that exclusively consist of the involved human cells in shape with a 3D architecture under the influence of an inflammatory microenvironment.

Prospectively, the established models will offer an alternative to the animal models used in basic and applied biomedical research in order to i) study pathophysiological and regenerative processes of musculoskeletal diseases, ii) identify new potential target molecules and iii) test new therapeutic strategies and finally iv) reduce or even replace animal experiments.

Keywords
Autoimmune diseases
Immunometabolism
Glucocorticoids
Fracture healing
3 R research

Glucocorticoids& Bioenergetica Prof. Dr. med. Frank Buttgereit Phone +49 (0)30 450 513 125 frank.buttgereit@charite.de more
Charité Liaison Group
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Groupleader:
Prof. Dr. med. Frank Buttgereit

Scientists:
Dr. rer. nat. Timo Gaber (Scientific head)
Dr. rer. nat. Cindy Strehl (Administrative head)
Dr. med. Sandra Hermann
Dr. vet. med. Annemarie Lang (PhD.)
Dr. med. Robert Biesen

PhD. Students:
Moritz Pfeiffenberger, MSc.
Alexandra Damerau, MSc.
Siska Wilantri, MSc.

MD/DVM/Master Students:
Lisa Ehlers
Pierre-Louis Krauß
Franziska Heinsohn
Edgar Wiebe
Antonia Brinkman
Angelique Wolter
Denise Dammann
Pelle Löwe
Aditi Kuppe

Bachelor Students:
Sümeyye Uzun 

Technicians:
Manuela Jakstadt
Gabriele May

Charité Liaison Group
Continue to Selected Publications
  • Gaber T, Brinkman ACK, Pienczikowski J, Diesing K, Damerau A, Pfeiffenberger M, Lang A, Ohrndorf S, Burmester GR, Buttgereit F, Hoff P. Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing. Int J Mol Sci. 2020 Jan 29;21(3). pii: E865. doi: 10.3390/ijms21030865. PubMed PMID: 32013232.
  • Strehl C, Ehlers L, Gaber T, Buttgereit F. Glucocorticoids-All-Rounders Tackling the Versatile Players of the Immune System. Front Immunol. 2019 Jul 24;10:1744. doi: 10.3389/fimmu.2019.01744. eCollection 2019. Review. PubMed PMID: 31396235; PubMed Central PMCID: PMC6667663
  • Pfeiffenberger M, Bartsch J, Hoff P, Ponomarev I, Barnewitz D, Thöne-Reineke C, Buttgereit F, Gaber T, Lang A. Hypoxia and mesenchymal stromal cells as key drivers of initial fracture healing in an equine in vitro fracture hematoma model. PLoS One. 2019 Apr 4;14(4):e0214276. doi: 10.1371/journal.pone.0214276. eCollection 2019. PubMed PMID: 30947253; PubMed Central PMCID: PMC6449067.
  • Gaber T, Chen Y, Krauß PL, Buttgereit F. Metabolism of T Lymphocytes in Health and Disease. Int Rev Cell Mol Biol. 2019;342:95-148. doi: 10.1016/bs.ircmb.2018.06.002. Epub 2018 Jul 18. Review. PubMed PMID: 30635095.
  • Lang A, Kirchner M, Stefanowski J, Durst M, Weber MC, Pfeiffenberger M, Damerau A, Hauser AE, Hoff P, Duda GN, Buttgereit F, Schmidt-Bleek K, Gaber T. Collagen I-based scaffolds negatively impact fracture healing in a mouse-osteotomy-model although used routinely in research and clinical application. Acta Biomater. 2019 Mar 1;86:171-184. doi: 10.1016/j.actbio.2018.12.043. Epub 2019 Jan 5. PubMed PMID: 30616076.
  • Gaber T, Strehl C, Buttgereit F. Metabolic regulation of inflammation. Nat Rev Rheumatol. 2017 May;13(5):267-279. doi: 10.1038/nrrheum.2017.37. Epub 2017 Mar 23. Review. PubMed PMID: 28331208.
  • Hahne M, Schumann P, Mursell M, Strehl C, Hoff P, Buttgereit F, Gaber T. Unraveling the role of hypoxia-inducible factor (HIF)-1α and HIF-2α in the adaption process of human microvascular endothelial cells (HMEC-1) to hypoxia: Redundant HIF-dependent regulation of macrophage migration inhibitory factor. Microvasc Res. 2018 Mar; 116:34-44. doi: 10.1016/j.mvr.2017.09.004. Epub 2017 Oct 6. PubMed PMID: 28993199.
  • Hoff P, Gaber T, Strehl C, Jakstadt M, Hoff H, Schmidt-Bleek K, Lang A, Röhner E, Huscher D, Matziolis G, Burmester GR, Schmidmaier G, Perka C, Duda GN, Buttgereit F. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients. Int J Mol Sci. 2017 Mar 8;18(3). pii: E583. doi: 10.3390/ijms18030583. PubMed PMID: 28282868; PubMed Central PMCID: PMC5372599.
  • Lang A, Volkamer A, Behm L, Röblitz S, Ehrig R, Schneider M, Geris L, Wichard J, Buttgereit F. In silico methods – Computational alternatives to animal testing. ALTEX. 2018;35(1):124-126. doi: 10.14573/altex.1712031. PubMed PMID: 29374440.
  • Cutolo M, Hopp M, Liebscher S, Dasgupta B, Buttgereit F. Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study. RMD Open. 2017 Mar 17;3(1): e000426. doi: 10.1136/rmdopen-2016-000426. eCollection 2017. PubMed PMID: 28405475; PubMed Central PMCID: PMC5372105.
Charité Liaison Group
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  • Gerd-Rüdiger Burmester, Thomas Häupl, Alexander Scheffold, Jacqueline Detert, Eugen Feist, Charité – Universitätsmedizin Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany
  • Georg N. Duda, Katharina Schmidt-Bleek, Charité – Universitätsmedizin Berlin, Berlin Brandenburg Center for Regenerative Therapies/ Julius-Wolff Institut, Berlin, Germany
  • Carsten Perka, Charité – Universitätsmedizin Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
  • Yvonne Dörffel, Charité – Universitätsmedizin Berlin, Department of Gastroenterology and Hepatology, Berlin, Germany
  • Nicole Pischon, Katharina Gurzawska, Charité – Universitätsmedizin Berlin, Centrum für Zahn-, Mund- und Kieferheilkunde, Abteilung für Parodontologie und Synoptische Zahnmedizin, Berlin, Germany
  • Andreas Radbruch, Max Löhning, Deutsches Rheuma-Forschungszentrum, Cell Biology, Berlin, Germany
  • Roland Lauster, TU-Berlin, Medical Biotechnology, Berlin, Germany
  • Markus Seibel, Hong Zhou, University of Sydney, ANZAC Institute, Sydney, Australia
  • Stefan Krauss, Beth Israel Deaconess Medical Center, Harvard Medical School, and Merck Research Laboratories, Boston, USA
  • Jon Yewdell, National Institute of Allergy and Infectious Diseases, Cellular Biology Section, Bethesda, USA
  • Christian Abraham, Andreas Brandt, medac GmbH, Wedel, Deutschland
  • Douglas J. Veale, University College Dublin, The Conway Institute for Biomedical and Biomolecular Research, Dublin, Ireland
  • Susanna Röblitz und Dr. Rainald Ehrig, Konrad-Zuse-Zentrum Berlin
  • Dirk Barnwitz und Dr. Igor Ponomarev, fzmb GmbH Bad Langensalza
  • Paulin Jirkof, Institut für Experimentelle Chirurgie, UniversitätsSpital Zürich, Universität Zürich
Charité Liaison Group
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