Abstract
Affective disorders (AD) including major depressive disorder (MDD) and bipolar disorder (BD) are common mood disorders associated with increased disability and poor health outcomes. Altered immune responses characterized by increased serum levels of pro-inflammatory cytokines and neuroinflammation are common findings in patients with AD and in corresponding animal models. Dendritic cells (DCs) represent a heterogeneous population of myeloid cells that orchestrate innate and adaptive immune responses and self-tolerance. Upon sensing exogenous and endogenous danger signals, mature DCs secrete proinflammatory factors, acquire migratory and antigen presenting capacities and thus contribute to neuroinflammation in trauma, autoimmunity, and neurodegenerative diseases. However, little is known about the involvement of DCs in the pathogenesis of AD. In this review, we summarize the current knowledge on DCs in peripheral immune responses and neuroinflammation in MDD and BD. In addition, we consider the impact of DCs on neuroinflammation and behavior in animal models of AD. Finally, we will discuss therapeutic perspectives targeting DCs and their effector molecules in mood disorders.
Highlights
pathogen-associated molecular patterns (PAMPs) binding to pattern-recognition receptors (PRRs) on Dendritic cells (DCs) and other innate immune cells induces a cascade of effector mechanisms involving phagocytosis and production of inflammatory factors, reactive oxygen species, and nitric oxide to eliminate the danger [55,56]
That CCR4+ DCs capable to invade the brain during neuroinflammation in a model of CNS autoimmunity are specialized to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) [159]
Another study showed that in vitro administration of desipramine, a norepinephrine reuptake inhibitor (NRI), reduced the secretion of TNF, IL-1β, and IL-12 by LPS-stimulated murine bone marrow-derived DCs [209]. These results indicate that the anti-inflammatory and immunomodulatory effects of fluoxetine and desipramine can be observed in murine DCs opening up the possibility to address the in vivo impact of these effects in animal models of depression-like behavior
Summary
BD is a severe and chronic recurrent mental disorder and is clinically characterized by extreme changes in mood, energy, and activity levels. The link between the immune system and depression was supported by reports showing that depressive symptoms occurred in patients after immunotherapy with type I interferons (IFN) [14,15] Since these authors and others have updated the hypothesis to include pathophysiological mechanisms such as oxidative stress, neurodegenerative processes, and altered neurogenesis in MDD [16,17,18]. To this end, clinical studies reporting phenotypic changes of DCs and their effector functions in individuals with depressive symptoms or diagnosed MDD and BD are reviewed. The potential of targeting DCs as a future treatment option of AD will be discussed
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