Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: Implications for neurodegeneration

Jonathan Kipnis, Michal Cardon, Hila Avidan, Gil M. Lewitus, Sharon Mordechay, Asya Rolls, Yael Shani, Michal Schwartz

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Fighting off neuronal degeneration requires a well controlled T-cell response against self-antigens residing in sites of the CNS damage. The ability to evoke this response is normally suppressed by naturally occurring CD4 +CD25+ regulatory T-cells (Treg). No physiological compound that controls Treg activity has yet been identified. Here, we show that dopamine, acting via type 1 dopamine receptors (found here to be preferentially expressed by Treg), reduces the suppressive activity and the adhesive and migratory abilities of Treg. Treg activity was correlated with activation of the ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway. Systemic injection of dopamine or an agonist of its type 1 receptors significantly enhanced, via a T-cell-dependent mechanism, protection against neuronal death after CNS mechanical and biochemical injury. These findings shed light on the physiological mechanisms controlling Treg and might open the way to novel therapeutic strategies for downregulating Treg activity (e.g., in neuronal degeneration) or for strengthening it (in autoimmune diseases).

Original languageEnglish
Pages (from-to)6133-6143
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number27
DOIs
StatePublished - Jul 7 2004

Keywords

  • Autoimmune response
  • CD4CD25 regulatory T-cells
  • CNS
  • Dopamine
  • Dopamine receptors
  • ERK1/2
  • Neurodegeneration
  • Neuroprotection
  • Neurotransmitters

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