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04-25-2008, 11:31 AM
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells
Journal home > Archive > Letter > Abstract
Letter abstract
Nature Medicine 13, 492 - 497 (2007)
Published online: 1 April 2007 | doi:10.1038/nm1561
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells
Katarzyna Maresz1,11, Gareth Pryce2,10,11, Eugene D Ponomarev1, Giovanni Marsicano3, J Ludovic Croxford2,4, Leah P Shriver1,5, Catherine Ledent6, Xiaodong Cheng1, Erica J Carrier7, Monica K Mann1,5, Gavin Giovannoni2,10, Roger G Pertwee8, Takashi Yamamura4, Nancy E Buckley9, Cecilia J Hillard7, Beat Lutz3, David Baker2,10,11 & Bonnie N Dittel1,5,11
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The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB1 and CB2 cannabinoid receptors in regulating CNS autoimmunity. We found that CB1 receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB2 receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB2-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher rate of proliferation and increased production of inflammatory cytokines, resulting in severe clinical disease. Together, our results demonstrate that the cannabinoid system within the CNS plays a critical role in regulating autoimmune inflammation, with the CNS directly suppressing T-cell effector function via the CB2 receptor.
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1. BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin 53226, USA.
2. Department of Neuroinflammation, Institute of Neurology, University College London, London WC1N 1PJ, UK.
3. Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany.
4. Department of Immunology, National Institute of Neuroscience, Tokyo 187-8502, Japan.
5. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
6. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Université libre de Bruxelles, B-1070 Brussels, Belgium.
7. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
8. Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
9. Biological Sciences Department, California State Polytechnic University, Pomona, California 91768, USA.
10. Present address: Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
11. These authors contributed equally to this work.
Correspondence to: Bonnie N Dittel1,5,11 e-mail: bonnie.dittel@bcw.edu
soul
Journal home > Archive > Letter > Abstract
Letter abstract
Nature Medicine 13, 492 - 497 (2007)
Published online: 1 April 2007 | doi:10.1038/nm1561
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells
Katarzyna Maresz1,11, Gareth Pryce2,10,11, Eugene D Ponomarev1, Giovanni Marsicano3, J Ludovic Croxford2,4, Leah P Shriver1,5, Catherine Ledent6, Xiaodong Cheng1, Erica J Carrier7, Monica K Mann1,5, Gavin Giovannoni2,10, Roger G Pertwee8, Takashi Yamamura4, Nancy E Buckley9, Cecilia J Hillard7, Beat Lutz3, David Baker2,10,11 & Bonnie N Dittel1,5,11
Top of page
The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB1 and CB2 cannabinoid receptors in regulating CNS autoimmunity. We found that CB1 receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB2 receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB2-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher rate of proliferation and increased production of inflammatory cytokines, resulting in severe clinical disease. Together, our results demonstrate that the cannabinoid system within the CNS plays a critical role in regulating autoimmune inflammation, with the CNS directly suppressing T-cell effector function via the CB2 receptor.
Top of page
1. BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin 53226, USA.
2. Department of Neuroinflammation, Institute of Neurology, University College London, London WC1N 1PJ, UK.
3. Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany.
4. Department of Immunology, National Institute of Neuroscience, Tokyo 187-8502, Japan.
5. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
6. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Université libre de Bruxelles, B-1070 Brussels, Belgium.
7. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
8. Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
9. Biological Sciences Department, California State Polytechnic University, Pomona, California 91768, USA.
10. Present address: Neuroimmunology Unit, Neuroscience Centre, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
11. These authors contributed equally to this work.
Correspondence to: Bonnie N Dittel1,5,11 e-mail: bonnie.dittel@bcw.edu
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