The 5-HT2B Receptor, the Immune System and Neuroinflammation

The defense against pathogens is mediated by innate and adaptive immune mechanisms that act in the periphery and in the central nervous system. In periphery, serotonin (5-HT) is synthesized in the gastrointestinal tract and the enteric nerves, and is stored in particularly high abundance in platelet granules. In the CNS, serotonin is synthesized by serotonergic neurons that innervate many brain areas and is stored in synaptic vesicles. Serotonin can regulate inflammation and immunity by acting at serotonin receptors that are differentially expressed on immune cells. Serotonin acts as a potent chemoattractant, recruiting innate immune cells to sites of inflammation, alters the production and release of cytokines and modulates immune cell activation/proliferation. In addition, serotonin has been widely involved in neuropsychiatric diseases, major depressive disorders, or autism spectrum disorders, and in neurodegenerative diseases, including Alzheimer’s disease or amyotrophic lateral sclerosis. Independent evidence suggests the contribution of inflammatory mediators in these pathologies. Indeed, peripheral infections as well as chronic diseases of the central nervous system cause activation of microglia, the resident macrophages of the brain. In this review, we summarize evidence that serotonin via 5-HT2B receptors regulates inflammation, either developmentally, acutely, or during neurodegenerative diseases, and in turn influences the course of these diseases through immune cell modulation.