06.08.21

Signaling Through the Type 2 Cannabinoid Receptor Regulates the Severity of Acute and Chronic Graft-Versus-Host Disease

In a recent study published in the journal Blood, researchers from the Medical College of Wisconsin have explored the role of a cannabinoid receptor on acute and chronic graft-versus-host disease (GVHD). The authors have found that signaling through the type 2 cannabinoid receptor (CB2R) is able to improve GVHD symptoms in a mouse model of GVHD.

GVHD is a serious condition which occurs after allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of certain blood cancers. The main driver of GVHD are donor T cells, which will attack the transplant recipient. The endocannabinoid system, specifically CB2R, plays an important role in regulating immune cells such as T cells. This study sought to understand the potential mechanism by which cannabinoid signaling can be used as a potential treatment for GVHD.

Using a donor mouse which does not have the CB2R gene, the researchers found that the recipient mice had less severe GVHD symptoms. Interestingly, CB2R was found to be significantly reduced on T cells during GVHD. Moreover, using drugs which increase CB2R activity such as THC and JWH-133, the authors were able to demonstrate that activating CB2R improved symptoms of aGVHD and cGVHD. Conversely, inhibiting CB2R increased the severity of GVHD. These findings have promise in the development of new GVHD treatments.

Reference:

Yuan CY, Zhou V, Sauber G, et al. Signaling through the type 2 cannabinoid receptor regulates the severity of acute and chronic graft-versus-host disease. Blood. 137(9):1241-1255 (2021). https://doi.org/10.1182/blood.2020004871

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