The emerging role of monocyte-derived cells in the central nervous system

Based on their ontogeny, tissue localization and functional specialization, monocyte-derived cells exhibit diverse phenotypic and functional properties. Monocyte-derived macrophages (moMAC) and dendritic cells (moDC) differentiate from common precursors in situ but carry out different regulatory functions in the periphery and the central nervous system (CNS). Under pathological conditions both moMACs and moDCs are known to be involved in inflammatory processes of the brain. The primary role of moDCs is to maintain self tolerance in the periphery as well as in the CNS and their subtypes and subsets are specialized for unique functional activities thus playing a pivotal role in bridging innate and adaptive immunity, orchestrating strictly controlled immune responses, and ensure restoration of the resting state or support the generation of regulatory, effector and memory T-lymphocytes. Depending on environmental cues, macrophages can be polarized to inflammatory and tissue regenerative/restorative directions that has a great impact on brain physiology. The strength, nature, combination and duration of tissue-derived molecular signals determine the functional activities of moMACs and moDCs and drive the polarization, magnitude, regulatory or stimulatory nature and duration of T-lymphocyte responses in both the periphery and the CNS.

Targeting monocyte-derived cells in the brain offers a promising and novel approach for the design of immunomodulatory strategies that may offer treatment options for neuropsychiatric diseases.