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

First Author  Gaffal E Year  2020
Journal  Int J Mol Sci Volume  21
Issue  2 PubMed ID  31940843
Mgi Jnum  J:289899 Mgi Id  MGI:6435223
Doi  10.3390/ijms21020475 Citation  Gaffal E, et al. (2020) Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity. Int J Mol Sci 21(2):475
abstractText  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.
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