Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis
Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differi...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001354 |
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| author | Mari Paz Serrano-Regal Celia Camacho-Toledano Inmaculada Alonso-García María Cristina Ortega Isabel Machín-Díaz Rafael Lebrón-Galán Jénnifer García-Arocha Leticia Calahorra Manuel Nieto-Díaz Diego Clemente |
| author_facet | Mari Paz Serrano-Regal Celia Camacho-Toledano Inmaculada Alonso-García María Cristina Ortega Isabel Machín-Díaz Rafael Lebrón-Galán Jénnifer García-Arocha Leticia Calahorra Manuel Nieto-Díaz Diego Clemente |
| author_sort | Mari Paz Serrano-Regal |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differing endogenous regenerative capacities of enrolled patients. In the experimental autoimmune encephalomyelitis (EAE) MS model, circulating monocytic myeloid-derived suppressor cells (M-MDSCs) are associated to milder disease courses, better recovery and less degree of tissue damage. Here, we show that disease severity affects the gradient of oligodendrocyte precursor cells (OPCs) present in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance. EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions. In addition, disease severity also impacts the abundance of newly generated oligodendrocytes throughout the EAE disease course. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated oligodendrocytes in the demyelinated lesions. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to new oligodendrocyte generation in response to an inflammatory insult. |
| format | Article |
| id | doaj-art-16fdbc33cab34b5891bcdc0733bfe525 |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-16fdbc33cab34b5891bcdc0733bfe5252025-08-20T02:56:09ZengElsevierNeurobiology of Disease1095-953X2025-06-0121010691910.1016/j.nbd.2025.106919Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosisMari Paz Serrano-Regal0Celia Camacho-Toledano1Inmaculada Alonso-García2María Cristina Ortega3Isabel Machín-Díaz4Rafael Lebrón-Galán5Jénnifer García-Arocha6Leticia Calahorra7Manuel Nieto-Díaz8Diego Clemente9Neuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Avd. Monforte de Lemos, 3-5, 28029 Madrid, SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Avd. Monforte de Lemos, 3-5, 28029 Madrid, SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Avd. Monforte de Lemos, 3-5, 28029 Madrid, SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Molecular Neuroprotection Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). SpainNeuroimmune-Repair Group, Hospital Nacional de Parapléjicos-SESCAM, Finca La Peraleda s/n, 45071 Toledo, Spain; Neuroimmune-Repair Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Avd. Monforte de Lemos, 3-5, 28029 Madrid, Spain; Corresponding author at: Grupo de Neuroinmuno-Reparación, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, E-45071 Toledo, Spain.Multiple sclerosis (MS) is a highly heterogeneous immune-mediated demyelinating disease. Myelin restoration is essential to prevent disability progression in MS patients. However, remyelinating therapies are failing in clinical trials, in part, due to the lack of biomarkers that classify the differing endogenous regenerative capacities of enrolled patients. In the experimental autoimmune encephalomyelitis (EAE) MS model, circulating monocytic myeloid-derived suppressor cells (M-MDSCs) are associated to milder disease courses, better recovery and less degree of tissue damage. Here, we show that disease severity affects the gradient of oligodendrocyte precursor cells (OPCs) present in mixed active-inactive lesions of MS patients, along with a positive correlation between M-MDSC density and OPC abundance. EAE disease severity negatively influences the density of total and newly generated OPCs found associated to the demyelinated lesions. In addition, disease severity also impacts the abundance of newly generated oligodendrocytes throughout the EAE disease course. Interestingly, circulating M-MDSCs at EAE onset and peak of the disease are directly associated to a higher density of newly generated oligodendrocytes in the demyelinated lesions. Our results set the basis for further studies on M-MDSCs as a promising new biomarker that identify a CNS prone to new oligodendrocyte generation in response to an inflammatory insult.http://www.sciencedirect.com/science/article/pii/S0969996125001354MyelinEAEMDSCsOPCsDemyelinationBiomarkers |
| spellingShingle | Mari Paz Serrano-Regal Celia Camacho-Toledano Inmaculada Alonso-García María Cristina Ortega Isabel Machín-Díaz Rafael Lebrón-Galán Jénnifer García-Arocha Leticia Calahorra Manuel Nieto-Díaz Diego Clemente Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis Neurobiology of Disease Myelin EAE MDSCs OPCs Demyelination Biomarkers |
| title | Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| title_full | Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| title_fullStr | Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| title_full_unstemmed | Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| title_short | Circulating myeloid-derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| title_sort | circulating myeloid derived suppressor cell load and disease severity are associated to an enhanced oligodendroglial production in a murine model of multiple sclerosis |
| topic | Myelin EAE MDSCs OPCs Demyelination Biomarkers |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125001354 |
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