Monocytes in central nervous system remyelination

Abstract

Remyelination failure with aging and progression of neurodegenerative disorders contributes to axonal dysfunction, highlighting the importance of understanding the mechanisms underpinning this process to develop regenerative therapies. Central nervous system (CNS) macrophages, encompassing both resident microglia and blood monocyte-derived cells, play a crucial role in driving successful remyelination.Although there has been a focus on the critical roles of microglia in remyelination, the specific contribution of monocyte-derived macrophages is still not fully understood. Until recently, the lack of tools enabling distinction between CNS macrophage populations has hindered our understanding of monocyte influence on remyelination.Recent advances have allowed for identification and characterization of monocyte populations in health, aging and in neurodegenerative conditions like multiple sclerosis, indicating heterogeneity of monocyte subsets impacted by both intrinsic and extrinsic factors. Here, we discuss the new tools enabling distinction between macrophage populations and advancements in understanding the importance of monocytes in remyelination, and reflect on the potential for therapeutic targeting of monocytes to promote remyelination.

Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis

“…Microglia communicate extensively with other cells through direct cellular interactions, ligand‐receptor interactions and extracellular vesicles. Harmonious intercellular communication involving microglia is important to maintain a healthy state of the tissue environment and to overcome pathology including neuroinflammation (Borst et al, 2021 ; Forbes & Miron, 2021 ; Ronzano et al, 2021 ). Our FACS analysis indicated that, during remission, the majority of myeloid and T cells that infiltrated from the periphery in the acute stage had been cleared from the CNS.…”

“…After injury, microglia acquire an activated, more phagocytic phenotype in response to cues from the environment (Keren‐Shaul et al, 2017 ; Krasemann et al, 2017 ; Kreutzberg, 1996 ). In MS, macrophages, including microglia, phagocytose myelin debris, modulate the extracellular matrix and secrete regenerative factors in order to create a favorable environment for oligodendrocyte progenitor cell (OPC) recruitment and OPC maturation, and therefore are relevant to remyelination (Forbes & Miron, 2021 ; Kotter et al, 2006 ; Lampron et al, 2015 ; Lloyd & Miron, 2019 ; Robinson & Miller, 1999 ). However, the extent to which microglia contribute to initiation and repair of MS lesions, especially in the secondary‐progressive phase has been poorly defined (Geladaris et al, 2021 ).…”

Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model

“…Microglia, peripheral monocytes/macrophages, and other innate immune cell types can both induce and resolve inflammation [ 23 , 24 ]. In the central nervous system (CNS), resident (microglia) and infiltrating innate immune cells coordinate a complex response toward the tissue repair.…”

Granulocyte–macrophage colony‐stimulating factor–stimulated human macrophages demonstrate enhanced functions contributing to T‐cell activation

“…Myeloid cells are abundant in MS lesions and perivascular infiltrates 1,3 . Blood monocytes infiltrating the CNS and then differentiating into macrophages, coined monocyte‐derived macrophages (MDMs), represent the majority of myeloid cells detected in MS lesions 4 . Macrophages and microglia shape the inflammatory milieu of the CNS via the production of numerous molecules 1,3 .…”

“…1,3 Blood monocytes infiltrating the CNS and then differentiating into macrophages, coined monocytederived macrophages (MDMs), represent the majority of myeloid cells detected in MS lesions. 4 Macrophages and microglia shape the inflammatory milieu of the CNS via the production of numerous molecules. 1,3 The characterization of these factors and the identification of the mechanisms driving their expression shed light on the plasticity and the large spectrum of phenotypes and functions myeloid cells possess (i.e.…”