PMID- 31940843 OWN - NLM STAT- MEDLINE DCOM- 20200603 LR - 20200603 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 2 DP - 2020 Jan 11 TI - Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity. LID - 10.3390/ijms21020475 [doi] LID - 475 AB - 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. FAU - Gaffal, Evelyn AU - Gaffal E AUID- ORCID: 0000-0002-4639-9841 AD - Department of Dermatology, University Hospital Magdeburg, 39104 Magdeburg, Germany. FAU - Kemter, Andrea M AU - Kemter AM AD - Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany. AD - Department of Pathology, The University of Chicago, Chicago, IL 60637, USA. FAU - Scheu, Stefanie AU - Scheu S AUID- ORCID: 0000-0002-9707-8191 AD - Institute of Medical Microbiology and Hospital Hygiene, University of Dusseldorf, 40225 Dusseldorf, Germany. FAU - Leite Dantas, Rafael AU - Leite Dantas R AUID- ORCID: 0000-0001-7358-990X AD - Department of Psychiatry, University of Munster, 48149 Munster, Germany. FAU - Vogt, Jens AU - Vogt J AD - Department of Psychiatry, University of Munster, 48149 Munster, Germany. FAU - Baune, Bernhard AU - Baune B AD - Department of Psychiatry, University of Munster, 48149 Munster, Germany. AD - Department of Psychiatry, The University of Melbourne, Melbourne 3010, Australia. AD - The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne 3010, Australia. FAU - Tuting, Thomas AU - Tuting T AD - Department of Dermatology, University Hospital Magdeburg, 39104 Magdeburg, Germany. FAU - Zimmer, Andreas AU - Zimmer A AD - Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany. FAU - Alferink, Judith AU - Alferink J AD - Department of Psychiatry, University of Munster, 48149 Munster, Germany. AD - Cells in Motion Interfaculty Centre, 48149 Muenster, Germany. LA - eng GR - DFG-FOR926 to JA, EG and AZ/Deutsche Forschungsgemeinschaft/ GR - DFG EXC 1003; Grant FF-2014-01 Cells in Motion-Cluster of Excellence to JA/Deutsche Forschungsgemeinschaft/ GR - SCHE692/3-1, SCHE692/4-1 to SS/Deutsche Forschungsgemeinschaft/ GR - DFG EXC 1023 Cluster of Excellence ImmunoSensation (EXC 1023) to AZ/Deutsche Forschungsgemeinschaft/ GR - Alf3/018/16 to JA/IZKF Munster/ GR - I-ST111423 and I-DL121204 to JA/IMF (University Munster)/ GR - Strategic Research Fund of the Heinrich Heine University Dusseldorf to SS/Strategic Research Fund of the Heinrich Heine University Dusseldorf/ PT - Journal Article DEP - 20200111 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (CNR1 protein, mouse) RN - 0 (Ccr4 protein, mouse) RN - 0 (Ccr7 protein, mouse) RN - 0 (Cnr2 protein, mouse) RN - 0 (Histocompatibility Antigens) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Receptor, Cannabinoid, CB2) RN - 0 (Receptors, CCR4) RN - 0 (Receptors, CCR7) RN - D241E059U6 (Dinitrofluorobenzene) SB - IM MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Chemotaxis MH - Dendritic Cells/cytology/*immunology MH - Dermatitis, Allergic Contact/genetics/*immunology MH - Dinitrofluorobenzene/toxicity MH - Histocompatibility Antigens/genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Receptor, Cannabinoid, CB1/genetics/metabolism MH - Receptor, Cannabinoid, CB2/genetics/*metabolism MH - Receptors, CCR4/genetics/metabolism MH - Receptors, CCR7/genetics/metabolism PMC - PMC7013892 OTO - NOTNLM OT - CB1 OT - CB2 OT - CCL19 OT - CXCL12 OT - MHC OT - allergic contact dermatitis OT - cannabinoid receptors OT - dendritic cells OT - hapten 2,4-dinitro-1-fluorobenzene OT - migration OT - skin inflammation COIS- The authors declare no conflict of interest. EDAT- 2020/01/17 06:00 MHDA- 2020/06/04 06:00 PMCR- 2020/01/01 CRDT- 2020/01/17 06:00 PHST- 2019/11/30 00:00 [received] PHST- 2020/01/03 00:00 [revised] PHST- 2020/01/07 00:00 [accepted] PHST- 2020/01/17 06:00 [entrez] PHST- 2020/01/17 06:00 [pubmed] PHST- 2020/06/04 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - ijms21020475 [pii] AID - ijms-21-00475 [pii] AID - 10.3390/ijms21020475 [doi] PST - epublish SO - Int J Mol Sci. 2020 Jan 11;21(2):475. doi: 10.3390/ijms21020475.