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Open AccessArticle

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

1
Department of Dermatology, University Hospital Magdeburg, 39104 Magdeburg, Germany
2
Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany
3
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
4
Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, 40225 Düsseldorf, Germany
5
Department of Psychiatry, University of Münster, 48149 Münster, Germany
6
Department of Psychiatry, The University of Melbourne, Melbourne 3010, Australia
7
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne 3010, Australia
8
Cells in Motion Interfaculty Centre, 48149 Muenster, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 475; https://doi.org/10.3390/ijms21020475
Received: 30 November 2019 / Revised: 3 January 2020 / Accepted: 7 January 2020 / Published: 11 January 2020
(This article belongs to the Special Issue Role of Dendritic Cells in Inflammation)
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. View Full-Text
Keywords: allergic contact dermatitis; dendritic cells; skin inflammation; CB1; CB2; cannabinoid receptors; hapten 2,4-dinitro-1-fluorobenzene; MHC; migration; CCL19; CXCL12 allergic contact dermatitis; dendritic cells; skin inflammation; CB1; CB2; cannabinoid receptors; hapten 2,4-dinitro-1-fluorobenzene; MHC; migration; CCL19; CXCL12
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Gaffal, E.; Kemter, A.M.; Scheu, S.; Leite Dantas, R.; Vogt, J.; Baune, B.; Tüting, T.; Zimmer, A.; Alferink, J. Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity. Int. J. Mol. Sci. 2020, 21, 475.

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