. 2021 May 18;22(10):5313. doi: 10.3390/ijms22105313

Table 1.

The effect of dopaminergic receptor targeting on EAE/MS pathogenesis and course.

Disease	Cell Type	The Effect of Dopaminergic Receptor Targeting	Authors
EAE	Splenic lymphocytes	D₂-like dopaminergic receptor agonist bromocriptine has a preventive and curative effect on EAE in mice. The treatment with bromocriptine reduces prolactin serum level and splenic lymphocyte proliferation upon Con A stimulation.	Riskind et al., 1991 [61]
EAE	Not investigated	The treatment with D₂-like dopaminergic receptor agonist bromocriptine reduces prolactin plasma level and clinical symptoms of acute and chronic EAE.	Dijkstra et al., 1993 [62]
EAE	Dendritic cells T cells	D₁-like dopaminergic receptor antagonist (SCH23390) has a preventive and curative effect on EAE in mice. D₂-like dopaminergic receptor antagonist (L750667) enhances EAE severity. The spleen cells from SCH23390-treated mice produce less IL-17 than the PBS-treated mice. Dendritic cells treated with SCH23390 and transferred to mice have the same effect compared with the direct influence of SCH23390 on EAE.	Nakano et al., 2008 [51]
EAE	Dendritic cells	D₅-dopaminergic receptor deficiency on dendritic cells impair LPS-induced IL-12 production and IL-23 mRNA expression and attenuate CD4⁺ T-cell activation. D₅-dopaminergic receptor deficient mice show a delayed onset of the EAE and reduced disease severity compared with WT mice. Transfer of D₅-dopaminergic receptor deficiency dendritic cells to EAE mice lessens the infiltration of Th17 cells in the CNS.	Prado et al., 2012 [52]
EAE	Peripheral lymphoid tissue	The treatment with a D₂- and D₃-dopaminergic receptors agonist pramipexole reduces IL-17, IL-1β and TNF-α production in lymph nodes and prevents clinical signs of the EAE in mice.	Lieberknecht et al., 2017 [41]
EAE	Dendritic cells	Transfer of D₅-dopaminergic-receptor-deficient dendritic cells to EAE mice reduces EAE manifestation and decreases the infiltration of IL-17⁺, IFN-γ⁺IL-17⁺ and GM-CSF⁺IFN-γ⁺IL-17⁺CD4⁺ T cells at the peak of the disease.	Prado et al., 2018 [53]
EAE	CD4⁺ T cells	D₅-dopaminergic receptor signaling in naive CD4⁺ T cells potentiates T cell activation with the acquisition of Th17-phenotype favoring EAE development. D₅-dopaminergic receptor signaling in Treg cells contributes to their suppressive activity.	Osorio-Barrios et al., 2018 [54]
RRMS Progressive MS	Not investigated	No evidence of clinical efficacy of bromocriptine therapy in MS. After one year of treatment, 14 of the 15 patients showed disease progression.	Bissay et al., 1994 [63]
RRMS	PBMCs CD4⁺ T cells CD8⁺ T cells	Dopamine (at 10⁻⁶ M) enhances IL-17 and IL-21 but suppresses IL-10 and TGF-β production by PHA-activated PBMCs in RRMS patients and enhances IL-17 production by anti-CD3/anti-CD28-antibody-activated CD4⁺ and CD8⁺ T cells in RRMS patients.	Ferreira et al., 2014 [64]
RRMS	CD3⁺ T cells	Dopamine (at 10⁻⁶ M) enhances IL-6, IL-17, IL-21, and IL-22 but suppresses IL-10 production by anti-CD3/anti-CD28-antibody-activated CD3⁺ T cells in RRMS patients.	Alvarenga-Filho et al., 2016 [23]
RRMS	PBMCs	Dopamine (at 10⁻⁵ M) suppresses IL-17 and IFN-γ production by anti-CD3/anti-CD28 microbead-activated PBMCs in RRMS patients and healthy subjects. Blockade of D₁-like dopaminergic receptor with SCH23390 enhances the inhibitory effect of dopamine on IL-17 production, while blockade of D₂-like dopaminergic receptor with sulpiride conversely reduces it.	Melnikov et al., 2016 [26]
RRMS	CD4⁺ T cells	Dopamine (at 10⁻⁵ M) suppresses IL-17 and IFN-γ production by anti-CD3/anti-CD28 microbead-activated CD4⁺ T cells in RRMS patients and healthy subjects. Blockade of D₂-like dopaminergic receptor with sulpiride reduces dopamine-mediated IL-17 suppression in MS patients. Blockade of D₁-like dopaminergic receptor with SCH23390 reduces IL-17 and GM-CSF production by activated CD4⁺ T cells in MS patients and in healthy subjects.	Melnikov et al., 2020 [37]