Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

Abstract

Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

“…Accumulating evidence points to the role of serotonergic components as immunomodulators working through the different 5HTRs. Depending on the 5HTR expressed in various leukocytes involved in the inflammatory response, platelet-derived 5-HT acts as an immune regulator in both the innate and adaptive immune systems [ 131 ]. 5-HT can stimulate Treg proliferation and regulate the function of B cells, natural killer cells, and neutrophils through the recruitment of DCs and monocytes to the inflammatory sites [ 132 , 133 ].…”

Tryptophan Metabolism, Inflammation, and Oxidative Stress in Patients with Neurovascular Disease

“…About 5% of TRP is metabolized to serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), melatonin (MEL), and to tryptamine (TA). Recently, 5-HT was identified as an activator of immune responses and inflammation [37,38] besides its role in neurotransmission, vasoconstriction, or vasodilation of blood vessels, control of hemostasis and platelet function [39]. MEL is frequently mentioned in connection with bodily rhythms and as an antioxidant lowering the OS [40].…”

Prognostic and immune regulating roles of YIF1B in Pan-Cancer: a potential target for both survival and therapy response evaluation

“…In particular, YIF1B has been shown to facilitate downstream signaling after combination of serotonin and HTR1A receptor in dendritic cells [12,13]. We propose that the immune cell infiltration data we observe, linked to expression of YIF1B, are related to serotonin's function in immune cell recruiting and differentiation [7]. Of note, expression of YIF1B was also related to expression of some specific immune checkpoint genes across several tumors.…”

“…Furthermore, the expression of 5-HTRs in immune cells has identified a role for serotonin in regulation of both innate and adaptive immune functions, such as inflammation and wound healing. Some drug targeting experiments have implicated serotonin in pathological autoimmune diseases and cancer, whereby it affects cell differentiation, tumor cell migration and metastatic spread [3][4][5][6][7]. Serotonin-induced signaling is, however, extremely complex, as would be expected given the multiplicity of its receptors, which include members of the GPCR family and ligand-gated ion channels.…”