Regulation of antigen-specific CTL and Th1 cell activation through 5-Hydroxytryptamine 2A receptor

Inoue, Makoto; Okazaki, Taro; Kitazono, Takako; Mizushima, Machiko; Omata, Masami; Ozaki, Shoichi

doi:10.1016/j.intimp.2010.10.007

Cited by 47 publications

(55 citation statements)

References 25 publications

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“…It is dramatically upregulated to augment early T cell activation events [20,28] . The expression of the 5-HT 2A receptor in both CD4 and CD8 T cells has been demonstrated [49] . The regulation exerted by 5-HT and other transmitters in T cell function and activity is autocrine and paracrine [19,20] .…”

Section: Discussionmentioning

confidence: 99%

“…This is initially mediated by 5-HT 7 , and the phosphorylation of extracellular signal-related kinase-1 and kinase-2 (ERK1/2) and inhibitor of NFκB in T cells [20] . The activation of T cells also leads to the increased expression of 5-HT 1B and 5-HT 2A , with the former promoting T-helper (Th) cell proliferation, which leads to the differentiation and functioning of immune cells [48,49] .…”

Section: Discussionmentioning

confidence: 99%

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Fluoxetine Treatment in Rats Increases the Rate of Taurine Transport in Mononuclear Cells

Colmenares-Aguilar

Urbina²,

Obregón³

et al. 2017

Neuroimmunomodulation

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Fluoxetine, a selective serotonin reuptake inhibitor antidepressant, modulates the mitogen-induced proliferation of lymphocytes. Lymphocytes contain taurine and express taurine transporter (TauT). Among the effects of taurine on lymphocytes are protection against oxidants and regulation of the inflammatory aspects of the immune response. Our aim was to determine the influence of fluoxetine treatment on taurine transport, and to determine the presence of TauT in the mononuclear cells of rats. Methods: Male adult Sprague-Dawley rats were treated with fluoxetine 10 mg/kg i.p. for 1, 2, and 3 weeks. The cells were obtained by density gradients. [³H]Taurine was used for transport assays. Amino acid levels were determined by high-performance liquid chromatography. Immunolabeling of CD4+, CD8+, and TauT was performed. The mRNA of TauT was evaluated by RT-PCR. Controls were included for each protocol. Results: The transport of taurine, after 1 week of treatment, was significantly augmented compared to controls. The affinity significantly increased at 1 and 2 weeks. While the percentage of CD4+ cells decreased and that of CD8+ cells increased, the percentage of TauT in CD4+ and CD8+ cells was not affected. Reduction of levels of aspartic acid, glutamic acid, threonine, alanine, glycine, and arginine occurred at 1 and 2 weeks. The taurine concentration significantly decreased after 2 and 3 weeks of treatment. The estimation of mRNA of TauT was not different. Conclusion: Taurine transport increases with fluoxetine treatment, and so this could be related to an immunomodulatory role of fluoxetine through TauT. Inhibition of serotonin reuptake might be involved in the regulation of taurine transport in mononuclear cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fluoxetine Treatment in Rats Increases the Rate of Taurine Transport in Mononuclear Cells

Colmenares-Aguilar

Urbina²,

Obregón³

et al. 2017

Neuroimmunomodulation

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“…Con A-mediated proliferation of rat blood lymphocytes is inhibited by antagonism of 5-HT 1A receptors, but it is not further elevated by agonists of this receptor [29], and Con A activation of spleen CD4+ and CD8+ T cells after 5-HT depletion is increased by 5-HT 2A receptor agonists [30]. The culture of lymphocytes in the presence of Con A increased the number of cells presenting 5-HT 7 receptors or tryptophan hydroxylase, indicating enhanced 5-HT transmission produced by lymphocyte activation.…”

Section: Discussionmentioning

confidence: 99%

5-HT<sub>7</sub> Receptors and Tryptophan Hydroxylase in Lymphocytes of Rats: Mitogen Activation, Physical Restraint or Treatment with Reserpine

Urbina

Arroyo²,

Lima³

2014

Neuroimmunomodulation

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Objectives: Serotonin (5-HT)₇ receptors in lymphocytes play a relevant role as modulators of T cell functions and might be modified by stress protocols. The aims of this work were to evaluate: (i) the presence of 5-HT₇ receptors in specific lymphocyte populations, (ii) the probable modifications of them by inflammatory stress with mitogen and (iii) the effects of physical and pharmacological stress. Methods: Blood lymphocytes were isolated by density gradients and differential adhesion to plastic. Concanavalin A (Con A) was systemically administered (500 μg/kg) or added to lymphocyte cultures (2.5 μg/ml, final volume 200 μl). Physical restraint was performed in Plexiglass boxes for 5 h per day for 5 days. Reserpine administration was 2.5 mg/kg for 3 days. Immunocytochemical labeling of CD4+, CD8+ and 5-HT₇ receptors, and also tryptophan hydroxylase cells was performed. mRNA of 5-HT₇ receptors was evaluated by RT-PCR. Controls were included for each protocol. Results: Con A treatment or culture exposure increased the number of lymphocytes expressing 5-HT₇ receptors or tryptophan hydroxylase, as compared to absence of the mitogen. Receptors were present in 12-16% of total rat lymphocytes, in ∼10% of CD4+ and in ∼5% of CD8+ cells from control rats. CD4+ decreased, and CD8+ and 5-HT₇ cells increased after physical restraint. Reserpine treatment elevated CD8+ and 5-HT₇ cells. Con A and physical restraint, but not reserpine treatment, significantly augmented 5-HT₇ receptor mRNA in lymphocytes. Conclusions: Rat lymphocytes, expressing tryptophan hydroxylase, could synthesize 5-HT, functioning as a direct autocrine modulator. The modifications of CD4+, CD8+ and 5-HT₇ receptors in lymphocytes by three stress protocols could have an impact on immune responses. In addition, the differential distribution of 5-HT₇ receptors indicates potential specific physiopathological roles.

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“…Thus the neurotransmitter participates in these two immune systems by influencing its cellular activity. One of the striking roles promoted by 5-HT includes T cell proliferation (Inoue et al, 2011;Yin et al, 2006) and modulation of the balance of T-helper (Th) cell subsets, i.e., Th1 and Th2 cells (Crews et al, 2006). Moreover, 5-HT stimulates mitogen-induced proliferation of B lymphocytes and thus promotes antibody responses as seen in autoimmunity (Iken et al, 1995).…”

Section: -Ht As An Immunoregulatormentioning

confidence: 99%

“…Interestingly, Carneiro et al (2009) investigated the effect of SERT functional coding variant, Glu-39 and Arg-152 haplotype, in inbred mouse lines and observed that this haplotype was associated with increased reuptake activity of the transporter protein, and displayed decreased T cell proliferation and T cell receptor expression. It is now a known fact that 5-HT promotes T-cell proliferation (Inoue et al, 2011;Yin et al, 2006). Under these circumstances, this haplotype possibly upregulates SERT activity, which in turn results in reduced 5-HT availability to carry out proper functioning of immune system.…”

Section: Sert and Inflammationmentioning

confidence: 99%

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders

Jaiswal

Mohanakumar

Rajamma

2015

Neuroscience & Biobehavioral Reviews

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Regulation of antigen-specific CTL and Th1 cell activation through 5-Hydroxytryptamine 2A receptor

Cited by 47 publications

References 25 publications

Fluoxetine Treatment in Rats Increases the Rate of Taurine Transport in Mononuclear Cells

Fluoxetine Treatment in Rats Increases the Rate of Taurine Transport in Mononuclear Cells

5-HT<sub>7</sub> Receptors and Tryptophan Hydroxylase in Lymphocytes of Rats: Mitogen Activation, Physical Restraint or Treatment with Reserpine

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders

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