Development of a Fluorescent Bodipy Probe for Visualization of the Serotonin 5-HT_1A Receptor in Native Cells of the Immune System

Abstract

Serotonin (5-HT) modulates key aspects of the immune system. However, its precise function and the receptors involved in the observed effects have remained elusive. Among the different serotonin receptors, 5-HT plays an important role in the immune system given its presence in cells involved in both the innate and adaptive immune responses, but its actual levels of expression under different conditions have not been comprehensively studied due to the lack of suitable tools. To further clarify the role of 5-HT receptor in the immune system, we have developed a fluorescent small molecule probe that enables the direct study of the receptor levels in native cells. This probe allows direct profiling of the receptor expression in immune cells using flow cytometry. Our results show that important subsets of immune cells including human monocytes and dendritic cells express functional 5-HT and that its activation is associated with anti-inflammatory signaling. Furthermore, application of the probe to the experimental autoimmune encephalomyelitis model of multiple sclerosis demonstrates its potential to detect the specific overexpression of the 5-HT receptor in CD4+ T cells. Accordingly, the probe reported herein represents a useful tool whose use can be extended to study the levels of 5-HT receptor in ex vivo samples of different immune system conditions.

Model‐Based Nanoengineered Pharmacokinetics of Iron‐Doped Copper Oxide for Nanomedical Applications

“…One major reason was the choice of the tumor model, for which checkpoint inhibition already has ag ood effect as as tandalone method, and neither of both methods (checkpoint inhibitor or anti-cancer agent) may intrinsically result in an activation of the immune system. [21] In this study,w el ook at the effect of epacadostat and the 6% Fe-doped CuO NPs for their combined therapy.The combination of epacadostat and 6% Fe-doped CuO NPs resulted in enhanced therapeutic efficacyand complete tumor remission, in contrast to animals treated with epacadostat and doxorubicin (Figure 4a-c). Repeated NP exposure at high dose (225 mg/mouse) showed absence of any clinical effects on blood biochemistry (Figure S8) while histological evaluation of major organs even showed the absence of macroscopic effects.S imilar to the cellular studies,the epacadostat and 6% Fe-doped CuO were equally effective against drug-resistant tumors (Figure 4d).…”

“…Epacadostat, a strong IDO1 inhibitor showed good preclinical results, but failed in a phase III clinical trial together with immune checkpoint inhibitors in metastatic melanoma. One major reason was the choice of the tumor model, for which checkpoint inhibition already has a good effect as a stand‐alone method, and neither of both methods (checkpoint inhibitor or anti‐cancer agent) may intrinsically result in an activation of the immune system . In this study, we look at the effect of epacadostat and the 6 % Fe‐doped CuO NPs for their combined therapy.…”

Immune Responses Regulated by Cannabidiol

“…99 Few of the CBDmediated effects acting through the serotonin 5-HT1a receptor have been reported in immune cells, but immune cells do express 5-HT1a. [100][101][102][103] One study showed that IL-1 produced in the brain in response to hypoxia-ischemia insult was inhibited by CBD, and reversed with the 5-HT1a receptor antagonist, WAY100635. 59 Studies have suggested that CBD might act through other receptors, including other TRP receptors, 66,85,[104][105][106][107] or opioid receptors.…”

hsa-miR-3177-5p and hsa-miR-3178 Inhibit 5-HT1A Expression by Binding the 3′-UTR Region in vitro

“…In addition, research on hsa-miR-3178 has mainly involved gastric cancer metastasis (Yang et al, 2014), gastric stromal tumor (Xiao et al, 2015), hepatocellular carcinoma (Li et al, 2015) and the immune system (Das et al, 2013). Interestingly, abnormal regulation of the serotonin system and 5-HT1A receptor has been implicated in gastrointestinal irritation (Sun et al, 2016) and changes in the immune system and inflammation (Hernández-Torres et al, 2018). Therefore, it was further identified that hsa-miR-3178 likely has an important regulatory function in affecting 5-HT1A receptor expression, which might cause susceptibility to neurological diseases.…”