title: Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.
abstract: Dendritic cells (DCs) are specifically equipped with the G protein-coupled receptor 34 (GPR34). Tight regulation of GPR34 gene expression seems highly important for proper immunological functions, because the absence of this receptor leads to an alteration of the immune response, whereas overexpression was reported to be involved in neuroinflammation. However, the regulatory mechanism of GPR34 expression has not yet been investigated. Whole-transcriptome RNA sequencing analysis from spleens and DCs of GPR34 knockout and wild-type mice, combined with protein-protein interaction data, revealed functional modules affected by the absence of this receptor. Among these, NF-κB, MAPK, and apoptosis-signaling pathways showed high significance. Using murine DCs we experimentally show that NF-κB and MAPK pathways are involved in the downregulation of GPR34. DCs lacking GPR34 have a higher caspase-3/7 activity and increased apoptosis levels. Our study reveals a novel role of GPR34 in the fate of DCs and identifies a regulatory mechanism that could be relevant for treatment of GPR34-overexpressing pathologies, such as neuroinflammatory or cancer conditions.
authors: Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; Rheumatology Unit, Department of Internal Medicine, University of Leipzig, 04103 Leipzig, Germany;
authors: Elisabeth
authors: E
authors: Jäger
authors: Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; and.
authors: Angela
authors: http://orcid.org/0000-0003-2336-1573
authors: A
authors: Schulz
authors: Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany;
authors: Vera
authors: V
authors: Lede
authors: Institute of Biomedical Informatics, National Yang-Ming University, Taipei 11221, Taiwan.
authors: Chen-Ching
authors: CC
authors: Lin
authors: Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; schoberg@medizin.uni-leipzig.de diana_leduc@eva.mpg.de.
authors: Torsten
authors: T
authors: Schöneberg
authors: Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; schoberg@medizin.uni-leipzig.de diana_leduc@eva.mpg.de.
authors: Diana
authors: http://orcid.org/0000-0001-7289-2552
authors: D
authors: Le Duc
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049312:Receptors, Lysophospholipid / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C118065:G-protein-coupled receptor 34; D049312:Receptors, Lysophospholipid