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.
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BibTeX
@article{angeli2026cd200,
title = {{CD200+ fibroblasts prime the immunoregulatory function of granulocytic myeloid-derived suppressor cells in inflammatory arthritis}},
author = {Mario R. Angeli and Christian Schütz and Hashem Schmidt and Richard Demmler and Jiyang Chang and Hannah Labinsky and Maria Gabriella Raimondo and Brikena Lalazi and Katerina Stergioula and Kaiyue Huang and Vladyslav Fedorchenko and Mohan Li and Zoltán Winter and Styliani Tsiami and Arnd Lienert and Sebastian Rütten and Stefanie Weber and Markus Luber and Tobias Bäuerle and Reza Bahrami and Heinrich Boehm and Georg Schett and Simon Rauber and Xenofon Baraliakos and Andreas Ramming},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78351-w},
url = {https://www.nature.com/articles/s41467-026-78351-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CD200+ fibroblasts prime the immunoregulatory function of granulocytic myeloid-derived suppressor cells in inflammatory arthritis
AU - Mario R. Angeli
AU - Christian Schütz
AU - Hashem Schmidt
AU - Richard Demmler
AU - Jiyang Chang
AU - Hannah Labinsky
AU - Maria Gabriella Raimondo
AU - Brikena Lalazi
AU - Katerina Stergioula
AU - Kaiyue Huang
AU - Vladyslav Fedorchenko
AU - Mohan Li
AU - Zoltán Winter
AU - Styliani Tsiami
AU - Arnd Lienert
AU - Sebastian Rütten
AU - Stefanie Weber
AU - Markus Luber
AU - Tobias Bäuerle
AU - Reza Bahrami
AU - Heinrich Boehm
AU - Georg Schett
AU - Simon Rauber
AU - Xenofon Baraliakos
AU - Andreas Ramming
PY - 2026
DA - 2026/10/13
JO - Nature Communications
DO - 10.1038/s41467-026-78351-w
UR - https://www.nature.com/articles/s41467-026-78351-w
AB - 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.
SN - 2041-1723
ER -