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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Leukoc+Biol
2015 ; 98
(3
): 435-47
Nephropedia Template TP
gab.com Text
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English Wikipedia
??-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and
delays skin graft rejection through activation of cannabinoid receptor 1 and
induction of myeloid-derived suppressor cells
#MMPMID26034207
Sido JM
; Nagarkatti PS
; Nagarkatti M
J Leukoc Biol
2015[Sep]; 98
(3
): 435-47
PMID26034207
show ga
Immune cells have been shown to express cannabinoid receptors and to produce
endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells
has been shown to trigger potent immunosuppression. Despite such studies, the
role of cannabinoids in transplantation, specifically to prevent allograft
rejection, has not, to our knowledge, been investigated previously. In the
current study, we tested the effect of THC on the suppression of HvGD as well as
rejection of skin allografts. To this end, we studied HvGD by injecting H-2(k)
splenocytes into H-2(b) mice and analyzing the immune response in the draining
ingLNs. THC treatment significantly reduced T cell proliferation and activation
in draining LNs of the recipient mice and decreased early stage
rejection-indicator cytokines, including IL-2 and IFN-?. THC treatment also
increased the allogeneic skin graft survival. THC treatment in HvGD mice led to
induction of MDSCs. Using MDSC depletion studies as well as adoptive transfer
experiments, we found that THC-induced MDSCs were necessary for attenuation of
HvGD. Additionally, using pharmacological inhibitors of CB1 and CB2 receptors and
CB1 and CB2 knockout mice, we found that THC was working preferentially through
CB1. Together, our research shows, for the first time to our knowledge, that
targeting cannabinoid receptors may provide a novel treatment modality to
attenuate HvGD and prevent allograft rejection.