The CB₂ receptor and its role as a regulator of inflammation

The CB₂ receptor is the peripheral receptor for cannabinoids. It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role. In this respect, the CB₂ receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases. In this regard, numerous studies have reported that mice lacking the CB₂ receptor have an exacerbated inflammatory phenotype. This suggests that therapeutic strategies aiming at modulating CB₂ signaling could be promising for the treatment of various inflammatory conditions. Herein, we review the pharmacology of the CB₂ receptor, its expression pattern, and the signaling pathways induced by its activation. We next examine the regulation of immune cell functions by the CB₂ receptor and the evidence obtained from primary human cells, immortalized cell lines, and animal models of inflammation. Finally, we discuss the possible therapies targeting the CB₂ receptor and the questions that remain to be addressed to determine whether this receptor could be a potential target to treat inflammatory disease.