Classically, microglial cells, responsible for homeostatic surveillance and orchestration of the tissue response to damage- and pathogen-associated molecular patterns, are viewed as the immune cells of the central nervous system (CNS). In the case of danger, damage or cell/tissue dyshomeostasis, microglia react with changes in process motility, polarization, directed process movement, morphology and gene expression profile; release pro- and anti-inflammatory mediators; proliferate; and clean brain parenchyma by means of phagocytosis. By doing so they frequently interact with other components of brain parenchyma, e.g. by pruning or stripping synaptic spines, thus contributing to (patho)physiological rewiring of neuronal circuits.

Macroglial cells so far have mostly been seen as targets of the immune cells during certain autoimmune reactions (e.g., myelin components during multiple sclerosis or aquaporin-4 during neuromyelitis optica) or an additional source of cytokines and chemokines, helping to sustain/amplify the immune reaction.

Nowadays, increasing evidence suggests that macroglial cells (astrocytes, oligodendrocytes and NG2-cells) may also exert a plenitude of additional immune functions. The underlying mechanisms are often related but not limited to glia-glia (macro-microglia) interactions. Under certain neuroinflammatory conditions, oligodendrocytes, as well as NG2-cells, can act as antigen-presenting cells. Astrocytes have been shown to phagocytose presynaptic boutons, thus contributing to synaptic rewiring. Microglia and astrocytes can secrete pro-inflammatory cytokines, promoting or inhibiting repair processes in their vicinity and modifying the extracellular matrix that also impacts the efficiency of e.g. myelin repair. Microglia increase the proliferation of NG2-cells after injury and generally regulate myelin growth and integrity.

Despite the paramount importance of these recent findings for basic and applied research, our understanding of the underlying mechanisms is incomplete.

In this article collection, we aim to bring together recent advances in understanding glia-glia interactions, with an emphasis on new research directions that decipher the role of glial cells in modulating immune responses.

This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Perspective, Case Report and Brief Research Report. We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• glia-glia interactions
• antigen presentation by macroglial cells
• cytokine and chemokine production by macroglial cells
• chemotactic behaviour of macroglial cells (in addition to microglial cells)
• migration of neuroglial cells in adult organisms (in healthy conditions as well as upon injury)
• phagocytosis of cells and subcellular compartments (e.g. synaptic pruning/stripping) by neuroglia
• macroglia-microglia immune crosstalk

The Topic Editors declare no competing interests with regard to the Research Topic subject.

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