An ARG1-associated immunometabolic program in bone marrow PMN-MDSC-like cells in multiple sclerosis and experimental autoimmune encephalomyelitis
- 1Department of Neurology, Tianjin Neurological Institute, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin and Ministry of Education, State Key Laboratory of Experimental Hematology, Tianjin Medical University General Hospital
- 2Thermoregulation and Inflammation Laboratory, Chengdu Medical College
- 3Department of Oncology, Laboratory of Immunity, Inflammation and Cancer, The First Affiliated Hospital of Chongqing Medical University
Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Recent work indicates that bone-marrow hematopoietic niches sense CNS autoimmunity and enhance myeloid output. However, whether MS bone marrow contains an immunometabolic PMN-MDSC-like state, and whether related ARG1-associated observations can be examined in a cross-species EAE context, remains unclear.
Methods: We reanalyzed single-cell RNA sequencing data from treatment-naive patients with MS and healthy controls, focusing on myeloid states. We used donor-aware proportion analysis, trajectory inference, module scoring, donor-pseudobulk pathway enrichment, expression-based transcription-factor prioritization, co-expression analysis, ligand-target inference, and ARG1 virtual perturbation. We also quantified flow-gated bone marrow PMN-MDSCs and ARG1 protein in MOG35-55-induced EAE and tested systemic prophylactic oral nor-NOHA.
Results: MS bone marrow showed myeloid skewing and a heterogeneous PMN-MDSC-like transcriptional state, while donor-level subtype proportions were comparable between groups. Neutrophil degranulation showed the strongest BH-supported donor-pseudobulk enrichment, and expression-based regulatory and communication analyses converged on an ARG1-associated network. In EAE, flow-gated bone-marrow PMN-MDSCs and ARG1 protein were increased, and systemic prophylactic nor-NOHA was associated with lower clinical scores and reduced spinal-cord pathology.
Conclusions: These data identify an ARG1-associated immunometabolic program in bone-marrow PMN-MDSC-like cells and connect the human transcriptional landscape with ARG1 protein expression and pharmacologic responses in EAE. Together, the findings establish ARG1-associated immunometabolism as a focused pathway for mechanistic and translational investigation.
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BibTeX
@article{xie2026arg1associated,
title = {{An ARG1-associated immunometabolic program in bone marrow PMN-MDSC-like cells in multiple sclerosis and experimental autoimmune encephalomyelitis}},
author = {Hengchang Xie and Yiwei Fu and Yingchun Bi and Ranran Han and Pengfei Liu and Bolin He and Baoting Chen and Honglei Ren},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1924483},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1924483/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An ARG1-associated immunometabolic program in bone marrow PMN-MDSC-like cells in multiple sclerosis and experimental autoimmune encephalomyelitis
AU - Hengchang Xie
AU - Yiwei Fu
AU - Yingchun Bi
AU - Ranran Han
AU - Pengfei Liu
AU - Bolin He
AU - Baoting Chen
AU - Honglei Ren
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1924483
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1924483/full
AB - Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Recent work indicates that bone-marrow hematopoietic niches sense CNS autoimmunity and enhance myeloid output. However, whether MS bone marrow contains an immunometabolic PMN-MDSC-like state, and whether related ARG1-associated observations can be examined in a cross-species EAE context, remains unclear. Methods: We reanalyzed single-cell RNA sequencing data from treatment-naive patients with MS and healthy controls, focusing on myeloid states. We used donor-aware proportion analysis, trajectory inference, module scoring, donor-pseudobulk pathway enrichment, expression-based transcription-factor prioritization, co-expression analysis, ligand-target inference, and ARG1 virtual perturbation. We also quantified flow-gated bone marrow PMN-MDSCs and ARG1 protein in MOG35-55-induced EAE and tested systemic prophylactic oral nor-NOHA. Results: MS bone marrow showed myeloid skewing and a heterogeneous PMN-MDSC-like transcriptional state, while donor-level subtype proportions were comparable between groups. Neutrophil degranulation showed the strongest BH-supported donor-pseudobulk enrichment, and expression-based regulatory and communication analyses converged on an ARG1-associated network. In EAE, flow-gated bone-marrow PMN-MDSCs and ARG1 protein were increased, and systemic prophylactic nor-NOHA was associated with lower clinical scores and reduced spinal-cord pathology. Conclusions: These data identify an ARG1-associated immunometabolic program in bone-marrow PMN-MDSC-like cells and connect the human transcriptional landscape with ARG1 protein expression and pharmacologic responses in EAE. Together, the findings establish ARG1-associated immunometabolism as a focused pathway for mechanistic and translational investigation.
SN - 1664-3224
ER -