In vivo monitoring of polymorphonuclear myeloid-derived suppressor cells in experimental rheumatoid arthritis
9 affiliations
- 1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University
- 2Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University
- 3Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, Eberhard Karls University
- 4Medical Proteome Center, Division for Experimental Ophthalmology, Institute for Ophthalmic Research, Eberhard Karls University
- 5Department of Pediatrics, Eberhard Karls University
- 6Department of Dermatology, Eberhard Karls University
- 7Institute of Pathology and Neuropathology, Eberhard Karls University
- 8Core Facility Histology, Faculty of Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen
- 9Department of Internal Medicine 2, University of Tubingen
Abstract
Introduction: Myeloid-derived suppressor cells (MDSCs) regulate immune responses, but their role in autoimmune diseases such as rheumatoid arthritis (RA) remains incompletely understood. Here, we applied non-invasive positron emission tomography (PET) imaging to investigate the migration dynamics of polymorphonuclear (PMN)-MDSCs in experimental RA.
Materials and methods: RA was induced in female BALB/c mice via K/BxN serum. Immune infiltrates in arthritic ankles were characterized by flow cytometry and liquid chromatography–mass spectrometry (LC–MS)-based proteomics. We radiolabeled bone marrow-derived (BM-PMN-MDSCs) and RA ankle-derived PMN-MDSCs (RA-PMN-MDSCs) intracellularly with [ ⁶⁴ Cu]Cu-PTSM or Ly6G-specific [ ⁶⁴ Cu]Cu-NOTA-1A8. Radiolabeled PMN-MDSCs were adoptively transferred into RA mice and tracked longitudinally by PET/MRI. In a second cohort, [ ⁶⁴ Cu]Cu-NOTA-1A8 was injected directly for in vivo imaging of Ly6G ⁺ myeloid cells over 48 h.
Results: RA progression was associated with a marked increase in the number of CD11b ⁺ Ly6C med Ly6G ⁺ PMN-MDSCs in arthritic ankles, whereas the number of CD11b ⁺ Ly6C high Ly6G ⁻ monocytic-MDSCs remained unchanged. PET/MRI demonstrated significantly enhanced homing of RA-PMN-MDSCs to inflamed ankles compared with that of BM-PMN-MDSCs, indicating disease-associated functional adaptation. Direct in vivo targeting of MDSCs with [ ⁶⁴ Cu]Cu-1A8 revealed strongly increased uptake in arthritic ankles at 1 h, 24 h, and 48 h p.i. , which was significantly reduced by Ly6G blockade, confirming tracer specificity. Proteomic analysis revealed enrichment of extracellular matrix organization and integrin signaling pathways in RA-PMN-MDSCs, suggesting that a distinct inflammatory signature underlies their migratory behavior.
Conclusion: PET/MRI enables non-invasive monitoring of PMN-MDSC migration during experimental RA and provides novel insights into the role of these cells in autoimmune inflammation, supporting the development of PMN-MDSCs as biomarkers and therapeutic targets in autoimmune diseases.
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BibTeX
@article{schwenck2026vivo,
title = {{In vivo monitoring of polymorphonuclear myeloid-derived suppressor cells in experimental rheumatoid arthritis}},
author = {Johannes Schwenck and Kerstin Fuchs and Mohamed Ali Jarboui and Sophia Geiger and Marc Neumann and Hasan H. Öz and Melanie Carevic and Sabrina Hoffmann and Dominik Hartl and Christoph M. Griessinger and Irene Gonzalez-Menendez and Leticia Quintanilla-Martinez and Jörg Henes and Gerald Reischl and Andreas Maurer and Bernd J. Pichler and Manfred Kneilling},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1909885},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1909885/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In vivo monitoring of polymorphonuclear myeloid-derived suppressor cells in experimental rheumatoid arthritis
AU - Johannes Schwenck
AU - Kerstin Fuchs
AU - Mohamed Ali Jarboui
AU - Sophia Geiger
AU - Marc Neumann
AU - Hasan H. Öz
AU - Melanie Carevic
AU - Sabrina Hoffmann
AU - Dominik Hartl
AU - Christoph M. Griessinger
AU - Irene Gonzalez-Menendez
AU - Leticia Quintanilla-Martinez
AU - Jörg Henes
AU - Gerald Reischl
AU - Andreas Maurer
AU - Bernd J. Pichler
AU - Manfred Kneilling
PY - 2026
DA - 2026/10/15
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1909885
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1909885/full
AB - Introduction: Myeloid-derived suppressor cells (MDSCs) regulate immune responses, but their role in autoimmune diseases such as rheumatoid arthritis (RA) remains incompletely understood. Here, we applied non-invasive positron emission tomography (PET) imaging to investigate the migration dynamics of polymorphonuclear (PMN)-MDSCs in experimental RA. Materials and methods: RA was induced in female BALB/c mice via K/BxN serum. Immune infiltrates in arthritic ankles were characterized by flow cytometry and liquid chromatography–mass spectrometry (LC–MS)-based proteomics. We radiolabeled bone marrow-derived (BM-PMN-MDSCs) and RA ankle-derived PMN-MDSCs (RA-PMN-MDSCs) intracellularly with [ ⁶⁴ Cu]Cu-PTSM or Ly6G-specific [ ⁶⁴ Cu]Cu-NOTA-1A8. Radiolabeled PMN-MDSCs were adoptively transferred into RA mice and tracked longitudinally by PET/MRI. In a second cohort, [ ⁶⁴ Cu]Cu-NOTA-1A8 was injected directly for in vivo imaging of Ly6G ⁺ myeloid cells over 48 h. Results: RA progression was associated with a marked increase in the number of CD11b ⁺ Ly6C med Ly6G ⁺ PMN-MDSCs in arthritic ankles, whereas the number of CD11b ⁺ Ly6C high Ly6G ⁻ monocytic-MDSCs remained unchanged. PET/MRI demonstrated significantly enhanced homing of RA-PMN-MDSCs to inflamed ankles compared with that of BM-PMN-MDSCs, indicating disease-associated functional adaptation. Direct in vivo targeting of MDSCs with [ ⁶⁴ Cu]Cu-1A8 revealed strongly increased uptake in arthritic ankles at 1 h, 24 h, and 48 h p.i. , which was significantly reduced by Ly6G blockade, confirming tracer specificity. Proteomic analysis revealed enrichment of extracellular matrix organization and integrin signaling pathways in RA-PMN-MDSCs, suggesting that a distinct inflammatory signature underlies their migratory behavior. Conclusion: PET/MRI enables non-invasive monitoring of PMN-MDSC migration during experimental RA and provides novel insights into the role of these cells in autoimmune inflammation, supporting the development of PMN-MDSCs as biomarkers and therapeutic targets in autoimmune diseases.
SN - 1664-3224
ER -