Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS is characterized by infiltrations of leukocytes such as T and B lymphocytes and macrophages. Macrophages have been identified as major effectors of inflammation and demyelination in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the activation and heterogeneity of macrophages in MS has been poorly investigated. Thus, in this study, we evaluated M1 and M2 macrophages immunophenotype from EAE and control mice by analyzing over 30 surface and intracellular markers through polychromatic flow cytometry, qRT-PCR, and ELISA assay. We showed that M1 macrophages possessed a higher proinflammatory profile in EAE compared to control mice, since they expressed higher levels of activation/co-stimulatory markers (iNOS, CD40, and CD80) and cytokines/chemokines (IL-6, IL-12, CCL2, and CXCL10), whereas M2 lost their M2-like phenotype by showing a decreased expression of their signature markers CD206 and CCL22, as well as a concomitant upregulation of several M1 makers. Furthermore, immunization of M1 and M2 macrophages with MOG35-55 led to a significant hyperactivation of M1 and a concomitant shift of anti-inflammatory M2 to pro-inflammatory M1 macrophages. Overall, we provide evidence for a phenotypic alteration of M1/M2 balance during MS, which can be of crucial importance not only for a better understanding of the immunopathology of this neurodegenerative disease but also to potentially develop new macrophage-centered therapeutic strategies.

Leuti, A., Talamonti, E., Gentile, A., Tiberi, M., Matteocci, A., Fresegna, D., et al. (2021). Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis. BIOMOLECULES, 11(6), 837 [10.3390/biom11060837].

Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis

Talamonti, Emanuela;Gentile, Antonietta;Fresegna, Diego;Centonze, Diego;
2021-06-04

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS is characterized by infiltrations of leukocytes such as T and B lymphocytes and macrophages. Macrophages have been identified as major effectors of inflammation and demyelination in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the activation and heterogeneity of macrophages in MS has been poorly investigated. Thus, in this study, we evaluated M1 and M2 macrophages immunophenotype from EAE and control mice by analyzing over 30 surface and intracellular markers through polychromatic flow cytometry, qRT-PCR, and ELISA assay. We showed that M1 macrophages possessed a higher proinflammatory profile in EAE compared to control mice, since they expressed higher levels of activation/co-stimulatory markers (iNOS, CD40, and CD80) and cytokines/chemokines (IL-6, IL-12, CCL2, and CXCL10), whereas M2 lost their M2-like phenotype by showing a decreased expression of their signature markers CD206 and CCL22, as well as a concomitant upregulation of several M1 makers. Furthermore, immunization of M1 and M2 macrophages with MOG35-55 led to a significant hyperactivation of M1 and a concomitant shift of anti-inflammatory M2 to pro-inflammatory M1 macrophages. Overall, we provide evidence for a phenotypic alteration of M1/M2 balance during MS, which can be of crucial importance not only for a better understanding of the immunopathology of this neurodegenerative disease but also to potentially develop new macrophage-centered therapeutic strategies.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26
eng
Con Impact Factor ISI
EAE
chemokines
cytokines
macrophages
multiple sclerosis
toll-like receptors
Animals
Cell Polarity
Encephalomyelitis, Autoimmune, Experimental
Female
Immunophenotyping
Macrophages
Mice
Mice, Inbred C57BL
Multiple Sclerosis
Neuronal Plasticity
https://www.mdpi.com/2218-273X/11/6/837
Leuti, A., Talamonti, E., Gentile, A., Tiberi, M., Matteocci, A., Fresegna, D., et al. (2021). Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis. BIOMOLECULES, 11(6), 837 [10.3390/biom11060837].
Leuti, A; Talamonti, E; Gentile, A; Tiberi, M; Matteocci, A; Fresegna, D; Centonze, D; Chiurchiù, V
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/282273
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