Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.
Nat Med. 2007-04-01; 13(4): 492-497
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1. Nat Med. 2007 Apr;13(4):492-7. Epub 2007 Apr 1.
Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor
CB1 on neurons and CB2 on autoreactive T cells.
Maresz K(1), Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, Ledent
C, Cheng X, Carrier EJ, Mann MK, Giovannoni G, Pertwee RG, Yamamura T, Buckley
NE, Hillard CJ, Lutz B, Baker D, Dittel BN.
(1)BloodCenter of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin
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.
PMID: 17401376 [Indexed for MEDLINE]