The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform
Rodrigo Pacheco - One of the best experts on this subject based on the ideXlab platform.
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Dopamine Receptor D5 Signaling Plays a Dual Role in Experimental Autoimmune Encephalomyelitis Potentiating Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T-Cells.
Frontiers in cellular neuroscience, 2018Co-Authors: Francisco Osorio-barrios, Carolina Prado, Francisco Contreras, Rodrigo PachecoAbstract:A number of studies have shown pharmacologic evidence indicating that stimulation of type I Dopamine Receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and in some other inflammatory disorders. Nevertheless, the lack of drugs that might discriminate between DRD1 and DRD5 has made the pharmacological distinction between the two Receptors difficult. We have previously shown genetic evidence demonstrating a relevant role of DRD5-signaling in dendritic cells (DCs) favoring the CD4+ T-cell-driven inflammation in EAE. However, the role of DRD5-signaling confined to CD4+ T-cells in the development of EAE is still unknown. Here, we analyzed the functional role of DRD5-signaling in CD4+ T-cell-mediated responses and its relevance in EAE by using a genetic approach. Our results show that DRD5-signaling confined to naive CD4+ T-cells exerts a pro-inflammatory effect promoting the development of EAE with a stronger disease severity. This pro-inflammatory effect observed for DRD5-signaling in naive CD4+ T-cells was related with an exacerbated proliferation in response to T-cell activation and to an increased ability to differentiate toward the Th17 inflammatory phenotype. On the other hand, quite unexpected, our results show that DRD5-signaling confined to Tregs strengthens their suppressive activity, thereby dampening the development of EAE manifestation. This anti-inflammatory effect of DRD5-signaling in Tregs was associated with a selective increase in the expression of glucocorticoid-induced tumor necrosis factor Receptor-related protein (GITR), which has been described to play a critical role in the expansion of Tregs. Our findings here indicate a complex role for DRD5-signaling in CD4+ T-cells-driven responses potentiating early inflammation mediated by effector T-cells in EAE, but exacerbating suppressive activity in Tregs and thereby dampening disease manifestation in late EAE stages.
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Dopamine Receptor D5 deficiency results in a selective reduction of hippocampal NMDA Receptor subunit NR2B expression and impaired memory.
Neuropharmacology, 2015Co-Authors: Rodrigo Moraga-amaro, Rodrigo Pacheco, Hugo González, Valentina Ugalde, Juan Pablo Donoso-ramos, Daisy Quintana-donoso, Marcelo Lara, Bernardo Morales, Patricio Rojas, Jimmy StehbergAbstract:Pharmacological evidence associates type I Dopamine Receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of Dopamine Receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two Receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA Receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways.
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Modulation of T-cell mediated immunity by Dopamine Receptor D5.
Endocrine metabolic & immune disorders drug targets, 2013Co-Authors: Carolina Prado, Sebastián Bernales, Rodrigo PachecoAbstract:CD4+ T-cells are central players orchestrating antigen-specific immunity and tolerance. Importantly, dendritic cells (DCs) are responsible for priming T-cells and for promoting their differentiation from naive T-cells into appropriate functional cells. Because of their fundamental roles in controlling immunity, activation and differentiation of DCs and CD4+ T-cells require tight regulatory mechanisms. Several studies have shown that Dopamine, not only mediates interactions into the nervous system, but it can also contribute to the modulation of immunity. Here, we review the emerging role of this neurotransmitter as a regulator of DCs and CD4+ T-cells physiology and its consequent involvement, in the regulation of immune response. We specially focus the analysis in the role of Dopamine Receptor D5 expressed on DCs and CD4+ T-cells in the modulation of immunity. We also discuss how alterations in the Dopamine-mediated regulation of immunity could contribute to the onset and development of immune-related disorders.
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Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity
Journal of immunology (Baltimore Md. : 1950), 2012Co-Authors: Carolina Prado, Sebastián Bernales, Francisco Contreras, Hugo González, Pablo Diaz, Daniela Elgueta, Magaly J. Barrientos, Andrés A. Herrada, Alvaro Lladser, Rodrigo PachecoAbstract:Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or Receptors remains poorly understood. In this study, we analyzed the role of Dopamine in the regulation of DC function. We found that DCs express Dopamine Receptors as well as the machinery necessary to synthesize, store, and degrade Dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4+ T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this Receptor in the modulation of a CD4+ T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4+ T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.
Carolina Prado - One of the best experts on this subject based on the ideXlab platform.
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Dopamine Receptor D5 Signaling Plays a Dual Role in Experimental Autoimmune Encephalomyelitis Potentiating Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T-Cells.
Frontiers in cellular neuroscience, 2018Co-Authors: Francisco Osorio-barrios, Carolina Prado, Francisco Contreras, Rodrigo PachecoAbstract:A number of studies have shown pharmacologic evidence indicating that stimulation of type I Dopamine Receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and in some other inflammatory disorders. Nevertheless, the lack of drugs that might discriminate between DRD1 and DRD5 has made the pharmacological distinction between the two Receptors difficult. We have previously shown genetic evidence demonstrating a relevant role of DRD5-signaling in dendritic cells (DCs) favoring the CD4+ T-cell-driven inflammation in EAE. However, the role of DRD5-signaling confined to CD4+ T-cells in the development of EAE is still unknown. Here, we analyzed the functional role of DRD5-signaling in CD4+ T-cell-mediated responses and its relevance in EAE by using a genetic approach. Our results show that DRD5-signaling confined to naive CD4+ T-cells exerts a pro-inflammatory effect promoting the development of EAE with a stronger disease severity. This pro-inflammatory effect observed for DRD5-signaling in naive CD4+ T-cells was related with an exacerbated proliferation in response to T-cell activation and to an increased ability to differentiate toward the Th17 inflammatory phenotype. On the other hand, quite unexpected, our results show that DRD5-signaling confined to Tregs strengthens their suppressive activity, thereby dampening the development of EAE manifestation. This anti-inflammatory effect of DRD5-signaling in Tregs was associated with a selective increase in the expression of glucocorticoid-induced tumor necrosis factor Receptor-related protein (GITR), which has been described to play a critical role in the expansion of Tregs. Our findings here indicate a complex role for DRD5-signaling in CD4+ T-cells-driven responses potentiating early inflammation mediated by effector T-cells in EAE, but exacerbating suppressive activity in Tregs and thereby dampening disease manifestation in late EAE stages.
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Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.
Frontiers in immunology, 2018Co-Authors: Carolina Prado, Hugo González, Alvaro Lladser, Valentina Ugalde, Michela Gaiazzi, Alicia Figueroa, Francisco Osorio-barrios, Ernesto López, Emanuela Rasini, Franca MarinoAbstract:The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of Dopamine Receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers. Importantly, ex vivo depletion of Dopamine from DCs resulted in a dramatic reduction of EAE severity, highlighting the relevance of an autocrine loop promoting inflammation in vivo. Mechanistic analyses indicated that DRD5-signalling in both mouse DCs and human monocytes involves the attenuation of signal transducer and activator of transcription 3-activation, a transcription factor that limits the production of the inflammatory cytokines interleukin (IL)-12 and IL-23. Furthermore, we found an exacerbated expression of all Dopamine Receptors in peripheral blood pro-inflammatory monocytes obtained from MS patients. These findings illustrate a novel mechanism by which myeloid antigen-presenting cells may trigger the onset of their inflammatory behaviour promoting the development of autoimmunity.
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Modulation of T-cell mediated immunity by Dopamine Receptor D5.
Endocrine metabolic & immune disorders drug targets, 2013Co-Authors: Carolina Prado, Sebastián Bernales, Rodrigo PachecoAbstract:CD4+ T-cells are central players orchestrating antigen-specific immunity and tolerance. Importantly, dendritic cells (DCs) are responsible for priming T-cells and for promoting their differentiation from naive T-cells into appropriate functional cells. Because of their fundamental roles in controlling immunity, activation and differentiation of DCs and CD4+ T-cells require tight regulatory mechanisms. Several studies have shown that Dopamine, not only mediates interactions into the nervous system, but it can also contribute to the modulation of immunity. Here, we review the emerging role of this neurotransmitter as a regulator of DCs and CD4+ T-cells physiology and its consequent involvement, in the regulation of immune response. We specially focus the analysis in the role of Dopamine Receptor D5 expressed on DCs and CD4+ T-cells in the modulation of immunity. We also discuss how alterations in the Dopamine-mediated regulation of immunity could contribute to the onset and development of immune-related disorders.
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Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity
Journal of immunology (Baltimore Md. : 1950), 2012Co-Authors: Carolina Prado, Sebastián Bernales, Francisco Contreras, Hugo González, Pablo Diaz, Daniela Elgueta, Magaly J. Barrientos, Andrés A. Herrada, Alvaro Lladser, Rodrigo PachecoAbstract:Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or Receptors remains poorly understood. In this study, we analyzed the role of Dopamine in the regulation of DC function. We found that DCs express Dopamine Receptors as well as the machinery necessary to synthesize, store, and degrade Dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4+ T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this Receptor in the modulation of a CD4+ T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4+ T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.
Hugo González - One of the best experts on this subject based on the ideXlab platform.
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Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.
Frontiers in immunology, 2018Co-Authors: Carolina Prado, Hugo González, Alvaro Lladser, Valentina Ugalde, Michela Gaiazzi, Alicia Figueroa, Francisco Osorio-barrios, Ernesto López, Emanuela Rasini, Franca MarinoAbstract:The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of Dopamine Receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers. Importantly, ex vivo depletion of Dopamine from DCs resulted in a dramatic reduction of EAE severity, highlighting the relevance of an autocrine loop promoting inflammation in vivo. Mechanistic analyses indicated that DRD5-signalling in both mouse DCs and human monocytes involves the attenuation of signal transducer and activator of transcription 3-activation, a transcription factor that limits the production of the inflammatory cytokines interleukin (IL)-12 and IL-23. Furthermore, we found an exacerbated expression of all Dopamine Receptors in peripheral blood pro-inflammatory monocytes obtained from MS patients. These findings illustrate a novel mechanism by which myeloid antigen-presenting cells may trigger the onset of their inflammatory behaviour promoting the development of autoimmunity.
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Dopamine Receptor D5 deficiency results in a selective reduction of hippocampal NMDA Receptor subunit NR2B expression and impaired memory.
Neuropharmacology, 2015Co-Authors: Rodrigo Moraga-amaro, Rodrigo Pacheco, Hugo González, Valentina Ugalde, Juan Pablo Donoso-ramos, Daisy Quintana-donoso, Marcelo Lara, Bernardo Morales, Patricio Rojas, Jimmy StehbergAbstract:Pharmacological evidence associates type I Dopamine Receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of Dopamine Receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two Receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA Receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways.
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Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity
Journal of immunology (Baltimore Md. : 1950), 2012Co-Authors: Carolina Prado, Sebastián Bernales, Francisco Contreras, Hugo González, Pablo Diaz, Daniela Elgueta, Magaly J. Barrientos, Andrés A. Herrada, Alvaro Lladser, Rodrigo PachecoAbstract:Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or Receptors remains poorly understood. In this study, we analyzed the role of Dopamine in the regulation of DC function. We found that DCs express Dopamine Receptors as well as the machinery necessary to synthesize, store, and degrade Dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4+ T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this Receptor in the modulation of a CD4+ T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4+ T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.
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Immunity on Dendritic Cells Potentiates Th17-Mediated Stimulation of Dopamine Receptor D5 Expressed
2012Co-Authors: Alvaro Lladser, Sebastián Bernales, Francisco Contreras, Daniela Elgueta, Magaly J. Barrientos, Hugo GonzálezAbstract:of March 27, 2012This information is current ashttp://www.jimmunol.org/content/188/7/3062 doi:10.4049/jimmunol.1103096February 2012;J Immunol 2012;188;3062-3070; Prepublished online 29€PachecoHerrada, Alvaro Lladser, Sebastian Bernales and RodrigoDiaz, Daniela Elgueta, Magaly Barrientos, Andres A. Carolina Prado, Francisco Contreras, Hugo Gonzalez, Pablo€
Francisco Osorio-barrios - One of the best experts on this subject based on the ideXlab platform.
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Dopamine Receptor D5 Signaling Plays a Dual Role in Experimental Autoimmune Encephalomyelitis Potentiating Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T-Cells.
Frontiers in cellular neuroscience, 2018Co-Authors: Francisco Osorio-barrios, Carolina Prado, Francisco Contreras, Rodrigo PachecoAbstract:A number of studies have shown pharmacologic evidence indicating that stimulation of type I Dopamine Receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and in some other inflammatory disorders. Nevertheless, the lack of drugs that might discriminate between DRD1 and DRD5 has made the pharmacological distinction between the two Receptors difficult. We have previously shown genetic evidence demonstrating a relevant role of DRD5-signaling in dendritic cells (DCs) favoring the CD4+ T-cell-driven inflammation in EAE. However, the role of DRD5-signaling confined to CD4+ T-cells in the development of EAE is still unknown. Here, we analyzed the functional role of DRD5-signaling in CD4+ T-cell-mediated responses and its relevance in EAE by using a genetic approach. Our results show that DRD5-signaling confined to naive CD4+ T-cells exerts a pro-inflammatory effect promoting the development of EAE with a stronger disease severity. This pro-inflammatory effect observed for DRD5-signaling in naive CD4+ T-cells was related with an exacerbated proliferation in response to T-cell activation and to an increased ability to differentiate toward the Th17 inflammatory phenotype. On the other hand, quite unexpected, our results show that DRD5-signaling confined to Tregs strengthens their suppressive activity, thereby dampening the development of EAE manifestation. This anti-inflammatory effect of DRD5-signaling in Tregs was associated with a selective increase in the expression of glucocorticoid-induced tumor necrosis factor Receptor-related protein (GITR), which has been described to play a critical role in the expansion of Tregs. Our findings here indicate a complex role for DRD5-signaling in CD4+ T-cells-driven responses potentiating early inflammation mediated by effector T-cells in EAE, but exacerbating suppressive activity in Tregs and thereby dampening disease manifestation in late EAE stages.
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Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.
Frontiers in immunology, 2018Co-Authors: Carolina Prado, Hugo González, Alvaro Lladser, Valentina Ugalde, Michela Gaiazzi, Alicia Figueroa, Francisco Osorio-barrios, Ernesto López, Emanuela Rasini, Franca MarinoAbstract:The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of Dopamine Receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4+ T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers. Importantly, ex vivo depletion of Dopamine from DCs resulted in a dramatic reduction of EAE severity, highlighting the relevance of an autocrine loop promoting inflammation in vivo. Mechanistic analyses indicated that DRD5-signalling in both mouse DCs and human monocytes involves the attenuation of signal transducer and activator of transcription 3-activation, a transcription factor that limits the production of the inflammatory cytokines interleukin (IL)-12 and IL-23. Furthermore, we found an exacerbated expression of all Dopamine Receptors in peripheral blood pro-inflammatory monocytes obtained from MS patients. These findings illustrate a novel mechanism by which myeloid antigen-presenting cells may trigger the onset of their inflammatory behaviour promoting the development of autoimmunity.
Sebastián Bernales - One of the best experts on this subject based on the ideXlab platform.
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Modulation of T-cell mediated immunity by Dopamine Receptor D5.
Endocrine metabolic & immune disorders drug targets, 2013Co-Authors: Carolina Prado, Sebastián Bernales, Rodrigo PachecoAbstract:CD4+ T-cells are central players orchestrating antigen-specific immunity and tolerance. Importantly, dendritic cells (DCs) are responsible for priming T-cells and for promoting their differentiation from naive T-cells into appropriate functional cells. Because of their fundamental roles in controlling immunity, activation and differentiation of DCs and CD4+ T-cells require tight regulatory mechanisms. Several studies have shown that Dopamine, not only mediates interactions into the nervous system, but it can also contribute to the modulation of immunity. Here, we review the emerging role of this neurotransmitter as a regulator of DCs and CD4+ T-cells physiology and its consequent involvement, in the regulation of immune response. We specially focus the analysis in the role of Dopamine Receptor D5 expressed on DCs and CD4+ T-cells in the modulation of immunity. We also discuss how alterations in the Dopamine-mediated regulation of immunity could contribute to the onset and development of immune-related disorders.
-
Stimulation of Dopamine Receptor D5 Expressed on Dendritic Cells Potentiates Th17-Mediated Immunity
Journal of immunology (Baltimore Md. : 1950), 2012Co-Authors: Carolina Prado, Sebastián Bernales, Francisco Contreras, Hugo González, Pablo Diaz, Daniela Elgueta, Magaly J. Barrientos, Andrés A. Herrada, Alvaro Lladser, Rodrigo PachecoAbstract:Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or Receptors remains poorly understood. In this study, we analyzed the role of Dopamine in the regulation of DC function. We found that DCs express Dopamine Receptors as well as the machinery necessary to synthesize, store, and degrade Dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4+ T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this Receptor in the modulation of a CD4+ T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4+ T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.
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Immunity on Dendritic Cells Potentiates Th17-Mediated Stimulation of Dopamine Receptor D5 Expressed
2012Co-Authors: Alvaro Lladser, Sebastián Bernales, Francisco Contreras, Daniela Elgueta, Magaly J. Barrientos, Hugo GonzálezAbstract:of March 27, 2012This information is current ashttp://www.jimmunol.org/content/188/7/3062 doi:10.4049/jimmunol.1103096February 2012;J Immunol 2012;188;3062-3070; Prepublished online 29€PachecoHerrada, Alvaro Lladser, Sebastian Bernales and RodrigoDiaz, Daniela Elgueta, Magaly Barrientos, Andres A. Carolina Prado, Francisco Contreras, Hugo Gonzalez, Pablo€