The aim of the work carried out by researchers in the »3D molecular pathology« project is to gain a better understanding of the influence of inflammatory cells on the course of diseases that trigger massive immune reactions. Furthermore, they aim to uncover the cellular and molecular mechanisms behind their emergence.
Sterile inflammations, which accompany for example heart attacks, strokes, cancer or autoimmune diseases, can also trigger massive inflammatory reactions in the body – also in the absence of direct influence by external factors. In this case, the immune system changes from a well-balanced state to a stressed and even uncontrolled and self-destructive state. Typical characteristics of this transition are, in addition to the functional changes that occur in activated immune cells, that these immune cells also infiltrate heavily inflamed tissue as inflammatory cells. It is also possible in this case for a general overreaction of the immune system to occur, which literally floods the body with inflammatory mediators, known as cytokines. This kind of cytokine storm can have fatal consequences in the absence of any intervention. Furthermore, inflammatory cells can also cause secondary tissue damage which further reinforces the pathological effects.
However, infiltrated immune cells can also have positive effects. They play a decisive role in tissue regeneration following a stroke, in the isolation of inflammation foci or in the monitoring and control of tumours, for example. In order to be able to assess the role an immune reaction plays in a sterile inflammation, it is therefore also important to consider the molecular context.
Molecular characterisation of inflammations for optimised therapies
Which local and systemic factors influence the inflammatory cells? Can the infiltration of these immune cells in affected tissue be selectively controlled? And can conclusions be drawn from this functional state about the physical condition of the organism? To answer these questions, the scientists trigger various medical conditions in animal models or investigate the cells of affected patients. Modern microscopy allows them to perform a 3D analysis of the inflamed tissue and the circulating or infiltrated immune cells. The molecular characteristics of the cells and tissue can subsequently be identified using flow cytometry, mass spectrometry (MS) and MS-based imaging.
In cooperation with Essen University Hospital, the scientists also analyse the reaction of the immune cells to comparable triggers in human samples. In their translational studies, the researchers investigate the response of human immune cells to comparable triggers or active ingredient libraries. The data is analysed and visualised using artificial intelligence. Based on the results, the project team aims to identify possible new targets for the treatment of cancer, stroke or heart attack, for example, and develop approaches for innovative treatment options.
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Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 44, No. 4, 2024, P. 915-929
Hagemann N, Qi Y, Mohamud Yusuf A, Li A, Squire A, Tertel T, Giebel B, Ludewig P, Spangenberg P, Chen J, Mosig A, Gunzer M, Hermann DM.
Microvascular Network Remodeling in the Ischemic Mouse Brain Defined by Light Sheet Microscopy
https://doi.org/10.1161/ATVBAHA.123.320339
Nature Communications, Vol. 14, 2023, P. 1-13
Cibir Z, Hassel J, Sonneck J, Kowitz L, Beer A, Kraus A, Hallekamp G, Rosenkranz M, Raffelberg P, Olfen S, Smilowski K, Burkard R, Helfrich I, Tuz…
ComplexEye:a multi-lens array microscope for high-throughput embedded immune cell migration analysis
https://doi.org/10.1038/s41467-023-43765-3
Proceedings of the National Academy of Sciences of the United States of America, Vol. 120, No. 40, 2023, P. e2215421120
Riehl DR, Sharma A, Roewe J, Murke F, Ruppert C, Eming SA, Bopp T, Kleinert H, Radsak MP, Colucci G, Subramaniam S, Reinhardt C, Giebel B, Prinz I,…
Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27
https://doi.org/10.1073/pnas.2215421120
Journal of Neuroinflammation, Vol. 20, 2023
Yin D, Wang C, Qi Y, Wang Y, Hagemann N, Mohamud Yusuf A, Dzyubenko E, Kaltwasser B, Tertel T, Giebel B, Gunzer M, Popa-Wagner A, Doeppner TR,…
Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhages
https://doi.org/10.1186/s12974-023-02894-8
JCI insight, Vol. 8, No. 13, 2023, P. e167482
Mittermüller D, Otto L, Long Z, Kraus A, Beer A, Hasenberg A, Zelinskyy G, Westmeier J, Hasenkrug KJ, Dittmer U, Gunzer M.
Regulatory T cells suppress the motility of cytotoxic T cells in Friend retrovirus-infected mice
https://doi.org/10.1172/jci.insight.167482
Liver International, Vol. 43, No. 4, 2022, P. 896-905
Langer M, Sichelschmidt S, Bauschen A, Guckenbiehl S, Bornemann L, Gunzer M, Lange CM.
Pathological neutrophil migration predicts adverse outcomes in hospitalized patients with liver cirrhosis
https://doi.org/10.1111/liv.15486
Frontiers in Immunology, Vol. 13, 2022, P. 1037330
Tuz AAA, Hasenberg A, Hermann DMM, Gunzer M, Singh V.
Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recovery
https://doi.org/10.3389/fimmu.2022.1037330
Nature Communications, Vol. 13, No. 1, 2022, P. 5786
Bretheau F, Castellanos-Molina A, Belanger D, Kusik M, Mailhot B, Boisvert A, Vallieres N, Lessard M, Gunzer M, Liu X, Boilard E, Quan N, Lacroix S.
The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury
https://doi.org/10.1038/s41467-022-33463-x
The Journal of allergy and clinical immunology, Vol. 150, No. 4, 2022, P. 909-919.e8
Adachi A, Honda T, Egawa G, Kanameishi S, Takimoto R, Miyake T, Hossain MR, Komine M, Ohtsuki M, Gunzer M, Ikuta K, Kabashima K.
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
https://doi.org/10.1016/j.jaci.2022.03.028
Basic Research in Cardiology, Vol. 117, No. 1, 2022
Mohamud Yusuf A, Hagemann N, Zhang X, Zafar M, Hussner T, Bromkamp C, Martiny C, Tertel T, Börger V, Schumacher F, Solari FA, Hasenberg M,…
Acid sphingomyelinase deactivation post-ischemia promotes brain angiogenesis and remodeling by small extracellular vesicles
https://doi.org/10.1007/s00395-022-00950-7
Cell Reports, Vol. 40, No. 7, 2022, P. 111171
Pylaeva E, Korschunow G, Spyra I, Bordbari S, Siakaeva E, Ozel I, Domnich M, Squire A, Hasenberg A, Thangavelu K, Hussain T, Goetz M, Lang KS, Gunzer…
During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes
https://doi.org/10.1016/j.celrep.2022.111171
Blood Advances, Vol. 6, No. 12, 2022, P. 3697-3702
Laroche A, Soulet D, Bazin M, Levesque T, Allaeys I, Vallières N, Gunzer M, Flamand L, Lacroix S, Boilard E.
Live imaging of platelets and neutrophils during antibody-mediated neurovascular thrombosis
https://doi.org/10.1182/bloodadvances.2021006728
Frontiers in Immunology, Vol. 13, 2022
Hussain T, Domnich M, Bordbari S, Pylaeva E, Siakaeva E, Spyra I, Ozel I, Droege F, Squire A, Lienenklaus S, Sutter K, Hasenberg A, Gunzer M, Lang S,…
IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes
https://doi.org/10.3389/fimmu.2022.878959
Frontiers in Immunology, Vol. 13, 2022, P. 823121
Haist M, Ries F, Gunzer M, Bednarczyk M, Siegel E, Kuske M, Grabbe S, Radsak M, Bros M, Teschner D.
Neutrophil-Specific Knockdown of β2 Integrins Impairs Antifungal Effector Functions and Aggravates the Course of Invasive Pulmonal Aspergillosis
https://doi.org/10.3389/fimmu.2022.823121
Journal of Virology, Vol. 96, No. 5, 2022, P. e0173021
Richter E, Bornemann L, Korencak M, Alter G, Schuster M, Esser S, Boesecke C, Rockstroh J, Gunzer M, Streeck H.
Reduction of CD8 T cell functionality but not inhibitory capacity by integrase inhibitors
https://doi.org/10.1128/JVI.01730-21
Science immunology, Vol. 7, No. 68, 2022, P. eabi9126
Özcan A, Collado-Diaz V, Egholm C, Tomura M, Gunzer M, Halin C, Kolios AGA, Boyman O.
CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection
https://doi.org/10.1126/sciimmunol.abi9126
European Heart Journal, Vol. 43, No. 4, 2022, P. 316-329
Michel L, Helfrich I, Hendgen-Cotta UB, Mincu R, Korste S, Mrotzek SM, Spomer A, Odersky A, Rischpler C, Herrmann K, Umutlu L, Coman C, Ahrends R,…
Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy
https://doi.org/10.1093/eurheartj/ehab430
BMC biology, Vol. 20, 2022
Le-Trilling VTK, Mennerich D, Schuler C, Sakson R, Lill JK, Kasarla SS, Kopczynski D, Loroch S, Flores-Martinez Y, Katschinski B, Wohlgemuth K,…
Identification of herbal teas and their compounds eliciting antiviral activity against SARS-CoV-2 in vitro
https://doi.org/10.1186/s12915-022-01468-z