The Effects of Serotonin in Immune Cells

Abstract

Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express at least one serotonin component. In recent years, a number of immunoregulatory functions have been ascribed to serotonin. In monocytes/macrophages, for example, serotonin modulates cytokine secretion. Serotonin can also suppress the release of tumor necrosis factor-α and interleukin-1β by activating serotonin receptors. Furthermore, neutrophil recruitment and T-cell activation can both be mediated by serotonin. These are only a few of the known immunomodulatory roles of serotonin that we will review here.

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

“…The strong link between inflammation, and disruptions of serotonin metabolism has been well complete set of components needed for serotonin production [80]. Dendritic cells, have also been found to mediate the release of proinflammatory cytokines, IL-1β and IL-8 via 5-HT3, 5-HT4, and 5-HT7 receptor subtypes [84].…”

Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T‐cell subsets in multiple sclerosis patients

“…It is also found in the gastrointestinal tract and enteric neurons, where it mediates the control of local physiological functions, such as peristaltic reflexes . In the immune system, serotonin, through different 5‐HT receptor (5‐HTR) subsets, modulates different functional profiles of mononuclear cells in a dose‐dependent manner . Furthermore, dendritic cells, by expressing the serotonin transporter, store this neurotransmitter into vesicles , which may modulate the behavior of T lymphocytes, the main cells implicated in MS pathogenesis.…”

Role of mast cells and basophils in pruritus

“…Mast cells are the more important source of serotonin in rodents, whereas serotonin is mostly found absent or expressed in marginal concentrations in human mast cells. However, mast cell serotonin levels can be upregulated in distinct pathologies such as carcinoid tumors or mastocytosis . In the intestine‐associated mesentery, the release of serotonin from mast cells is at least in parts under control of pruritogenic SP/CGRP/VIP‐positive nerve fibers closely associated to mast cells .…”

“…IL-31Rα (m) 168 (h), 225 OSMR (m) 169 Delayed onset of itch in humans; 175 Involved in chronic itch of AD patients; 226 OSM treatment initiates mast cell growth 227 (Continues) or mastocytosis. 39,[44][45][46] In the intestine-associated mesentery, the release of serotonin from mast cells is at least in parts under control of pruritogenic SP/CGRP/VIP-positive nerve fibers closely associated to mast cells. 47 This microanatomical association is also probable in human skin tissue but not established.…”