Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity

Abstract

Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2−/− and Cnr1−/−/Cnr2−/− bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1−/− DCs. In vitro stimulated Cnr2−/− DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2−/− DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2−/− DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.

The Immune Endocannabinoid System of the Tumor Microenvironment

“…Human DCs express CB 1 and CB 2 receptors and also produce AEA and 2-AG [ 146 ], suggesting potential effects on the TME. CB 2 has been recently reported to influence dendritic cell maturation [ 230 ]. Another innate immune cell population with cannabinoid receptor expression is NK cells [ 16 ], which are well linked to tumor regression [ 231 ].…”

Cutaneous Squamous Cell Carcinoma and Lichen Simplex Chronicus Successfully Treated with Topical Cannabinoid Oil: A Case Report and Summary of Cannabinoids in Dermatology

“…Topical cannabinoids can be associated with cutaneous adverse events, such as allergic contact dermatitis and contact urticaria (Table 8) [10][11][12][13][14][15][16]. A study of dispensaries in Los Angeles, California, discovered that 84% of over-the-counter topical cannabinoids had one or more North American contact dermatitis group (NACDG) allergens [17].…”

Endocannabinoid System and Tumour Microenvironment: New Intertwined Connections for Anticancer Approaches

“…Several studies demonstrated that human DCs expressed CBRs and produced eCBs [ 12 , 251 ]. In the pancreatic ductal adenocarcinoma murine model, 2-AG administration exhibited a direct anti-tumour effect by inducing DC phenotypic maturation and the production of pro-inflammatory cytokines, but also significantly promoted an immunosuppressive microenvironment via increasing the suppressive immune cell population of myeloid-derived suppressor cells (MDSCs) [ 252 ].…”