EN
Project - B07:
X Ray Fluorescence Imaging (XFI) of immune cells and soluble molecules in the liver
Project leaders:
Dr. rer. nat. Neus Feliu
Prof. Dr. rer. nat. Florian Grüner
Lidia Bosurgi, PhD
Summary
A growing body of evidence in both preclinical and clinical studies indicates that monocyte dysfunction is central to disease progression in various liver diseases, from acute and chronic liver failure to infection-mediated liver damage and autoimmunity. Consequently, tightly regulating monocyte recruitment to the damaged liver is essential for appropriate healing. The advent of fate mapping and single-cell sequencing has significantly contributed to define population dynamics and transcriptional heterogeneity among distinct monocyte populations. However, the trafficking dynamics of monocytes to the liver are still unclear to a large extent. Gaining a better and deeper understanding of this process could help identify specific monocyte clusters with distinct homing potential and provide crucial information on migration kinetics, which could be essential for potential future interventional therapies. Advanced X-ray Fluorescence Imaging (XFI) is a novel and promising full-body, non-invasive imaging method that enables in vivo tracking of various entities such as immune cells, drug compounds, mRNA-carrying nanoparticles, and even antibodies. XFI offers unique advantages over existing imaging methods and can thus be used to gain new, as yet inaccessible data. Our previous data indicate that tracking of labelled macrophages in mice using XFI is feasible and can provide information about the biodistribution of injected immune cells with high spatial resolution at high sensitivity levels. This breakthrough paves the way for a better mechanistic understanding of the biodistribution, trafficking and fate of immune cells at preclinical and later clinical stages. Based on this, our main hypothesis is that advanced XFI can facilitate understanding of the dynamics of immune cell recruitment to the liver in vivo. In particular, we postulate that alterations in cell trafficking of selected monocyte subpopulations can influence the progression of liver diseases. We will test this hypothesis by synthesising and characterising biocompatible novel labels and contrast agents for XFI to optimise the labelling and tracking of monocytes, either labelled ex vivo and adoptively transferred into the recipient host or labelled directly in vivo. Additionally, by using select XFI antibodies, we will track in vivo endogenous soluble molecules, such as cytokines and chemokines, and correlate their accumulation with monocyte trafficking and their potential contribution to liver pathophysiology. Together, these data will provide unprecedented temporal insights into the liver’s immune response.
Project plan
Our hypothesis is that advanced XFI can facilitate the understanding of the dynamics of monocyte recruitment to the liver. In particular, we hypothesise that introducing XFI as a novel tracking method for distinct monocyte subpopulations and the corresponding secreted cytokines/chemokines will increase our understanding of how these subpopulations contribute to the development and regulation of liver inflammation.
We plan to test this hypothesis through two distinct work packages (WPs):
WP1: To investigate the dynamics of monocyte trafficking to the liver via XFI upon monocyte ex vivo labelling.
WP2: To dissect the migration dynamics of monocyte subpopulations and their contribution to the regulation of liver inflammation through “in vivo labelling” via XFI.
Project related publications
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong MN, Kylies D, K. Grafe SK, Edenhofer I, Aranda Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm AB, Richardt U, Eggert P, Tappe D, Weidemann S, Ghosh S, Krebs K, Alonso Gonzalez N, Worthmann A, Lohse AW, Huber S, Rothlin CV, Puelles VG, Jacobs T, Gagliani N#, Bosurgi L#. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science 2024; 384, eabo7027 (2024). DOI: 10.1126/science.abo7027.
Staufer T, Kornig C, Liu B, Liu Y, Lanzloth C, Schmutzler O, Bedke T, Machicote A, Parak WJ, Feliu N, Bosurgi L, Huber S, Grüner F. Enabling X-ray fluorescence imaging for in vivo immune cell tracking. Sci Rep 2023; 13: 11505. doi.org/10.1038/s41598-023-38536-5. Open access.
Staufer T, Grüner F. Development and Recent Advances in Biomedical X-ray Fluorescence Imaging. Int J Mol Sci 2023;24(13):10990. doi: 10.3390/ijms241310990. Open access.
Grüner F, Blumendorf F, Schmutzler O, Staufer T, Bradbury M, Wiesner U, Rosentreter T, Loers G, Lutz D, Richter B, Fischer M, Schulz F, Steiner S, Warmer M, Burkhardt A, Meents A, Kupinski M, Hoeschen C. Localising functionalised gold-nanoparticles in murine spinal cords by X-ray fluorescence imaging and background-reduction through spatial filtering for human-sized objects. Sci Rep 2018; 8: 16561. doi:10.1038/s41598-018-34925-3. Open access.
Liu Y, Kornig C, Qi B, Schmutzler O, Staufer T, Sanchez-Cano C, Magel E, White JC, Feliu N, Grüner F, Parak WJ. Size- and Ligand-Dependent Transport of Nanoparticles in Matricaria chamomilla as Demonstrated by Mass Spectroscopy and X-ray Fluorescence Imaging. ACS Nano 2022; 16: 12941-51. doi:10.1021/acsnano.2c05339. Open access.
Kornig C, Staufer T, Schmutzler O, Bedke T, Machicote A, Liu B, Liu Y, Gargioni E, Feliu N, Parak WJ, Huber S, Grüner F. In-situ x-ray fluorescence imaging of the endogenous iodine distribution in murine thyroids. Sci Rep 2022; 12: 2903. doi:10.1038/s41598-022-06786-4. Open access.
Schmutzler O, Graf S, Behm N, Mansour WY, Blumendorf F, Staufer T, Kornig C, Salah D, Kang Y, Peters JN, Liu Y, Feliu N, Parak WJ, Burkhardt A, Gargioni E, Gennis S, Chandralingam S, Hoeg F, Maison W, Rothkamm K, Schulz F, Grüner F. X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumour Cell Microsamples. Int J Mol Sci 2021; 22:3691. doi: 10.3390/ijms22073691. Open access.
Sun X GM, Nold P, Said A, Pelaz B, Schmied F, von Pückler K, Chakraborty I, Figiel J, Zhao Y, Brendel C, Hasssan M, Parak WJ, Feliu N. Tracking stem cells and macrophages with gold and iron oxide nanoparticles. The choice of the best suited particles. Apply Materials Today 2019; 15, 267-279. doi: 10.1016/J.APMT.2018.12.006.
Liu Z EA, Carrillo-Carrion, C, Chakraborty, I, Zhu, D, Gallego M, Parak, WJ, Feliu N. Biodegradation of bi-labelled polymer-coated rare-earth nanoparticles in adherent cell cultures. Chemistry of Materials 2020; 32, 1, 245-254. doi: 10.1021/acs.chemmater.9b03673.
Yan H, Cacioppo M, Megahed S, Arcudi F, Dordevic L, Zhu D, Schulz F, Prato M, Parak WJ, Feliu N. Influence of the chirality of carbon nanodots on their interaction with proteins and cells. Nat Commun 2021; 12: 7208. doi: 10.1038/s41467-021-27406-1. Open access.
# equally contributing authors