title: Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
abstract: 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 CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-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 CB(2) receptor.
authors.affiliation: BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin 53226, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maresz
authors.forename: Gareth
authors.initials: G
authors.lastname: Pryce
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Ponomarev
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: J Ludovic
authors.initials: JL
authors.lastname: Croxford
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Carrier
authors.forename: Monica K
authors.initials: MK
authors.lastname: Mann
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Roger G
authors.initials: RG
authors.lastname: Pertwee
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Buckley
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Bonnie N
authors.initials: BN
authors.lastname: Dittel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism*; D017931:DNA Primers; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C469526:Cnr2 protein, rat; D017931:DNA Primers; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2