Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity

Carolina Prado, Francisco Contreras, Hugo González, Pablo Díaz, Daniela Elgueta, Magaly Barrientos, Andrés A. Herrada, Álvaro Lladser, Sebastián Bernales, Rodrigo Pacheco

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

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 wildtype 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.

Original languageEnglish
Pages (from-to)3062-3070
Number of pages9
JournalJournal of Immunology
Volume188
Issue number7
DOIs
Publication statusPublished - 1 Apr 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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