The role of D2-like dopaminergic receptors in dopamine-mediated modulation of TH17-cells in multiple sclerosis

Background and aims: miRNAs, as a class of non-coding RNAs, take part in different cellular processes. Dysregulation of different miRNAs has been reported in numerous disorders to date. Multiple sclerosis (MS) is an autoimmune disease with high prevalence in Iran and Th17 cells play an important role in its pathogenesis. In the current study, we aimed to predict the possible role of miR-34a and miR-215 in the process of controlling Th17 differentiation, and hence, their possible impact on the onset and progression of MS. Methods: We investigated probable interactions of miRNAs and genes that participate in Th17 cells differentiation using miRwalk database as an integrative one which utilizes 10 different algorithms to predict miRNA-mRNA interaction. Results: Based on our findings, miR-34a and miR-215 were predicted to have a potential role in the induction of Th17 cells differentiation. Conclusion: Conclusively, miR-34a and miR-215 may up-regulate Th17 cells of MS patients. Since bioinformatics data have shown that these miRNAs suppress negative regulatory genes in Th17 cells differentiation, we suppose that down-regulation of these miRNAs could ameliorate MS symptoms. Therefore, several therapeutic approaches may be considered for these miRNAs besides their application as valuable prognostic/diagnostic biomarkers in detection of various stages of MS.

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Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis

Mediators of Inflammation ◽

10.1155/2015/475158 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

Elisabetta Volpe ◽

Luca Battistini ◽

Giovanna Borsellino

Keyword(s):

Multiple Sclerosis ◽

Cell Biology ◽

Th17 Cells ◽

Bacterial Infections ◽

Demyelinating Diseases ◽

T Helper ◽

Pathogenic Role ◽

T Helper 17 ◽

Effector Cytokines

The discovery of the T helper (Th) 17 lineage, involved in the protection against fungal and extracellular bacterial infections, has profoundly revolutionized our current understanding of T cell-mediated responses in autoimmune diseases, including multiple sclerosis (MS). Indeed, recent data demonstrate the pathogenic role of Th17 cells in autoimmune disorders. In particular, studies in MS and in its animal model (EAE, experimental autoimmune encephalomyelitis) have revealed a crucial role of Th17 cells in the pathogenesis of autoimmune demyelinating diseases in both mice and humans. Over the past years, several important aspects concerning Th17 cells have been elucidated, such as the factors which promote or inhibit their differentiation and the effector cytokines which mediate their responses. The identification of the features endowing Th17 cells with high pathogenicity in MS is of particular interest, and discoveries in Th17 cell biology and function could lead to the design of new strategies aimed at modulating the immune response in MS. Here, we will discuss recent advances in this field, with particular focus on the mechanisms conferring pathogenicity in MS and their potential modulation.

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The role of TH17 cells in multiple sclerosis: Therapeutic implications

Autoimmunity Reviews ◽

10.1016/j.autrev.2020.102647 ◽

2020 ◽

Vol 19 (10) ◽

pp. 102647 ◽

Cited By ~ 2

Author(s):

Tobias Moser ◽

Katja Akgün ◽

Undine Proschmann ◽

Johann Sellner ◽

Tjalf Ziemssen

Keyword(s):

Multiple Sclerosis ◽

Th17 Cells ◽

Therapeutic Implications

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The role of Th17 cells in patients with relapsing-remitting multiple sclerosis: Interleukin-17A and interleukin-17F serum levels

Immunology Letters ◽

10.1016/j.imlet.2015.01.001 ◽

2015 ◽

Vol 164 (2) ◽

pp. 76-80 ◽

Cited By ~ 37

Author(s):

Zohreh Babaloo ◽

Mohammad Reza Aliparasti ◽

Farhad Babaiea ◽

Shohreh Almasi ◽

Behzad Baradaran ◽

...

Keyword(s):

Multiple Sclerosis ◽

Th17 Cells ◽

Serum Levels ◽

Interleukin 17A ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis ◽

Interleukin 17F

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The role of D2-like dopaminergic receptor in dopamine-mediated modulation of Th17-cells in multiple sclerosis

Current Neuropharmacology ◽

10.2174/1570159x19666210823103859 ◽

2021 ◽

Vol 19 ◽

Author(s):

Mikhail Melnikov ◽

Anastasiya Sviridova ◽

Vladimir Rogovskii ◽

Vladimir Kudrin ◽

Vladimir Murugin ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Healthy Subjects ◽

Th17 Cells ◽

Cell Activity ◽

Interleukin 17 ◽

Dopaminergic Receptor ◽

Gm Csf ◽

Ifn Γ

: Dopamine is a direct mediator of neuroimmune interaction and may play a significant role in multiple sclerosis (MS) pathogenesis by modulating immune cell activity and cytokine production. We studied the effects of dopamine on Th17-cells function in 34 patients with relapsing-remitting MS and 23 healthy subjects. Production of interleukin-17 (IL-17), interferon-γ (IFN-γ), granulocyte-colony stimulating factor (GM-CSF), and IL-21 by CD4+ T-cells as well as dopamine were comparable between the groups. Dopamine suppressed IL-17, IFN-γ, GM-CSF, and IL-21 production by stimulated СD4+ T-cells in both groups. Blockade of D1-like dopaminergic receptor with a specific antagonist SCH23390 did not affect dopamine-mediated cytokine suppression. In contrast, blockade of D2-like dopaminergic receptor by sulpiride decreased dopamine's inhibitory effect on IL-17 secretion in both groups and GM-CSF and IL-21 production in MS patients. Blockade of D1-like dopaminergic receptor directly inhibited IL-17, IFN-γ, GM-CSF in both groups and IL-21 production in healthy subjects, while blockade of D2-like dopaminergic receptor had no effect on cytokine secretion. Finally, activation of D2-like dopaminergic receptor with a specific agonist quinpirole decreased IL-17, IFN-γ, and GM-CSF production in both groups. These data suggest an inhibitory role of dopamine on Th17-cells in MS, which could be mediated by the activation of D2-like dopaminergic receptor.

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