title: Dopamine receptors D3 and D5 regulate CD4(+)T-cell activation and differentiation by modulating ERK activation and cAMP production.
abstract: Dopamine receptors have been described in T-cells, however their signalling pathways coupled remain unknown. Since cAMP and ERKs play key roles regulating T-cell physiology, we aim to determine whether cAMP and ERK1/2-phosphorylation are modulated by dopamine receptor 3 (D3R) and D5R, and how this modulation affects CD4(+) T-cell activation and differentiation. Our pharmacologic and genetic evidence shows that D3R-stimulation reduced cAMP levels and ERK2-phosphorylation, consequently increasing CD4(+) T-cell activation and Th1-differentiation, respectively. Moreover, D5R expression reinforced TCR-triggered ERK1/2-phosphorylation and T-cell activation. In conclusion, these findings demonstrate how D3R and D5R modulate key signalling pathways affecting CD4(+) T-cell activation and Th1-differentiation.
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Dafne
authors.initials: D
authors.lastname: Franz
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Contreras
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Hugo
authors.initials: H
authors.lastname: González
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Prado
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Elgueta
authors.affiliation: Departamento de Ciencias Biológicas y Químicas, Facultad de Ciencia, Universidad San Sebastián, Providencia, 7510157 Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Figueroa
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile. Electronic address: rpacheco@cienciavida.org.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pacheco
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D053645:Interleukin-2 Receptor alpha Subunit; D050637:Receptors, Dopamine D3; D050641:Receptors, Dopamine D5; D015759:Ionomycin; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Dopamine receptors; Knockout mice; Neuroimmunology; T-cell activation; TCR signalling; Th1 differentiation