CD200+ fibroblasts prime the immunoregulatory function of granulocytic myeloid-derived suppressor cells in inflammatory arthritis
Abstract Granulocytic myeloid-derived suppressor cells (G-MDSCs) are immunoregulatory cells of the neutrophil lineage. Here, we show that immunoregulation by G-MDSCs is imprinted by the joint tissue microenvironment in patients with axial spondyloarthritis and in animal models of inflammatory arthritis. We demonstrate that the suppressive function of G-MDSCs is significantly enhanced in the joint tissue, but not in the circulation. Analysis of public single-cell RNA sequencing datasets was consistent with Cd200r1 high Hmgb2 + precursors differentiating into G-MDSCs following interaction with Cd200 + fibroblasts. In hTNFtg/ Il23mc mice, treatment with a CD200R1 agonist promoted an immunoregulatory signature associated with PD-L1 expression, whereas CD200 blockade reversed the phenotype. Following adoptive transfer of G-MDSC precursor cells into arthritic mice, administration of a CD200-blocking antibody impaired the differentiation of PD-L1 + G-MDSCs and exacerbated disease severity. These findings reveal a tissue-intrinsic program that facilitates resolution of inflammation through fibroblast-myeloid crosstalk that enhances G-MDSC function.
Authors
- Zoltán Winter (ORCID: https://orcid.org/0000-0003-4119-9637)
- Markus Luber (ORCID: https://orcid.org/0000-0003-1895-5481)
- Styliani Tsiami (ORCID: https://orcid.org/0000-0003-2624-7485)
- Mario Raphael Angeli (ORCID: https://orcid.org/0000-0002-2911-4269)
- Kaiyue Huang
- Jiyang Chang (ORCID: https://orcid.org/0000-0002-3646-2878)
- Richard Demmler (ORCID: https://orcid.org/0009-0004-3476-2481)
- Maria Gabriella Raimondo (ORCID: https://orcid.org/0000-0003-2020-6711)
- Christian Schütz (ORCID: https://orcid.org/0000-0002-2361-2785)
- Andreas Ramming (ORCID: https://orcid.org/0000-0002-7003-501X)
- Simon Rauber (ORCID: https://orcid.org/0000-0001-8306-9334)
- Arnd Lienert
- Georg Andreas Schett (ORCID: https://orcid.org/0000-0001-8740-9615)
- Hannah Labinsky (ORCID: https://orcid.org/0000-0001-5762-9182)
- Sebastian Rütten
- Vladyslav Fedorchenko (ORCID: https://orcid.org/0000-0003-4695-4937)
- Brikena Lalazi (ORCID: https://orcid.org/0000-0002-3333-7211)
- Mohan Li (ORCID: https://orcid.org/0000-0001-7677-0675)
- Stefanie Weber (ORCID: https://orcid.org/0000-0001-8592-2810)
- Katerina Stergioula
- Hashem Schmidt
- Heinrich Boehm
- Reza Bahrami (ORCID: https://orcid.org/0009-0005-6299-5546)
- Xenofon Baraliakos
- Tobias Bäuerle
Institutions
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Johannes Gutenberg University Mainz (DE)
- University of Würzburg (DE)
- Universitätsklinikum Erlangen (DE)
- Rheumazentrum Ruhrgebiet (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Augenklinik Universitätsklinikum Würzburg (DE)
- Zentralklinik Bad Berka (DE)
- Universitätsklinikum Würzburg (DE)
- Comprehensive Cancer Center Erlangen (DE)
- St. Anna Hospital (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-13
- DOI
- https://doi.org/10.1038/s41467-026-78351-w
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Federation of Pharmaceutical Industries and Associations
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Gottfried Wilhelm Leibniz Universität Hannover