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

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jonathan KipnisMichal Schwartz

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).

Citations

Jan 26, 2006·Cancer Immunology, Immunotherapy : CII·Kerstin LangKurt S Zaenker
Apr 3, 2010·Cancer Immunology, Immunotherapy : CII·Tobias BoppHansjörg Schild
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Michal SchwartzJonathan Kipnis
Mar 5, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Peter J GaskillJoan W Berman
Aug 13, 2009·Journal of Ocular Biology, Diseases, and Informatics·Michal Schwartz, Anat London
Jan 5, 2010·Journal of Ocular Biology, Diseases, and Informatics·Michal Schwartz, Anat London
Mar 28, 2013·Neurotoxicity Research·Arik EisenkraftArseny Finkelstein
Jan 20, 2010·ACS Chemical Neuroscience·Nuska TschammerPeter Gmeiner
Oct 31, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Li ChenSavio L C Woo
Jul 19, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Maurizio GiorelliMaria Trojano
Apr 25, 2006·Journal of Neurotrauma·Michal Schwartz, Eti Yoles
Jun 30, 2009·Journal of Lipid Research·Akadiri YessoufouNaim Akhtar Khan
Sep 7, 2012·PloS One·Judith A PotashkinAlexey A Leontovich
Nov 16, 2012·PloS One·Krishna E TobónEldo V Kuzhikandathil
Dec 22, 2010·Indian Journal of Ophthalmology·Sushil K VasudevanJonathan G Crowston
Aug 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jonathan KipnisMichal Schwartz
Jul 12, 2011·Trends in Molecular Medicine·James T Walsh, Jonathan Kipnis
Dec 1, 2007·Injury·Sven K Tschoeke, Wolfgang Ertel
Oct 2, 2007·Brain, Behavior, and Immunity·Yaniv Ziv, Michal Schwartz
Dec 23, 2015·BioMed Research International·Jian-Hua LuYi-Hua Qiu
Jun 11, 2005·Immunology·Elizabeth J MeredithJohn Gordon
Aug 30, 2005·Annals of the New York Academy of Sciences·Michal Schwartz, Jonathan Kipnis
Apr 9, 2009·Movement Disorders : Official Journal of the Movement Disorder Society·Davide MartinoJames F Leckman
Aug 18, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Feng He, Rudi Balling
Apr 24, 2014·The European Journal of Neuroscience·Enida Kuric, Karsten Ruscher
Jul 28, 2004·Trends in Pharmacological Sciences·Michal Schwartz, Jonathan Kipnis
Feb 14, 2006·Trends in Molecular Medicine·Jonathan KipnisMichal Schwartz
Jan 13, 2006·Trends in Neurosciences·Michal SchwartzUwe-Karsten Hanisch
Apr 9, 2016·Journal of Neuroinflammation·Josefine R ChristiansenVanesa Sanchez-Guajardo
May 5, 2016·Stem Cells International·Odette LeiterTara L Walker
Jan 15, 2013·Neuroscience and Biobehavioral Reviews·Mady Hornig, W Ian Lipkin
Jan 3, 2014·Clinical & Developmental Immunology·Nathalie DeckxNathalie Cools
Dec 26, 2012·Immunobiology·Mohieddin JafariMoncef Zouali
Aug 12, 2014·Brain Research·Anthony J FilianoJonathan Kipnis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.