Abstract
Astrocytes and oligodendrocytes are known to play critical roles in the central nervous system development, homeostasis and response to injury. In addition to their well-defined functions in synaptic signaling, blood-brain barrier control and myelination, it is now becoming clear that both glial cells also actively produce a wide range of immune-regulatory factors and engage in an intricate communication with neurons, microglia or with infiltrated immune cells, thus taking a center stage in both inflammation and resolution processes occurring within the brain. Resolution of inflammation is operated by the superfamily of specialized pro-resolving lipid mediators (SPMs), that include lipoxins, resolvins, protectins and maresins, and that altogether activate a series of cellular and molecular events that lead to spontaneous regression of inflammatory processes and restoration of tissue homeostasis. Here, we review the manifold effects of SPMs on modulation of astrocytes and oligodendrocytes, along with the mechanisms through which they either inhibit inflammatory pathways or induce the activation of protective ones. Furthermore, the possible role of SPMs in modulating the cross-talk between microglia, astrocytes and oligodendrocytes is also summarized. This SPM-mediated mechanism uncovers novel pathways of immune regulation in the brain that could be further exploited to control neuroinflammation and neurodegeneration.
Highlights
Reviewed by: Marta Fumagalli, University of Milan, Italy Francesca Boscia, University of Naples Federico II, Italy
Resolution of inflammation is operated by the superfamily of specialized pro-resolving lipid mediators (SPMs), that include lipoxins, resolvins, protectins and maresins, and that altogether activate a series of cellular and molecular events that lead to spontaneous regression of inflammatory processes and restoration of tissue homeostasis
For a long time it was believed that the acute response to inflammation both in the periphery and in the central nervous system (CNS) passively dissipated over time due to a reduced production of inflammatory mediators from either resident non-neuronal cells or infiltrated leukocytes; it has been more recently appreciated that in the brain termination of neuroinflammation is kept in homeostatic balance by the active process of resolution, orchestrated by several families of SPMs, and that results in the maintenance of brain homeostasis and avoidance of neurodegeneration and subsequent development of neurodegenerative diseases
Summary
Inflammation is a self-limited and protective process that usually resolves on its own and restores tissue homeostasis. The biosynthesis of maresins (MaR1 and MaR2) is operated by 12-LOX in humans and by 12/15LOX in mice from 14(S)-HDHA intermediate, which is recognized as marker of maresins (Serhan et al, 2009; Deng et al, 2014) The bioaction of these 3 classes of DHA-derived SPMs are shared in common with those of the other SPMs because they reduce leukocyte infiltration, induce pathogen killing, promote the clearance of debris and dead cells by the process of efferocytosis and reduce production of pro-inflammatory mediators and enhance that of anti-inflammatory ones. As suggested by their name, their physiological function is to orchestrate host responses and promote tissue regeneration and resolution of infections and has been demonstrated in different model organisms (Serhan et al, 2018)
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