Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.

Autor:	Jäger E; Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; Rheumatology Unit, Department of Internal Medicine, University of Leipzig, 04103 Leipzig, Germany;, Schulz A; 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., Lede V; Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany;, Lin CC; Institute of Biomedical Informatics, National Yang-Ming University, Taipei 11221, Taiwan., Schöneberg T; Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; schoberg@medizin.uni-leipzig.de diana_leduc@eva.mpg.de., Le Duc D; Institute of Biochemistry, University of Leipzig, 04103 Leipzig, Germany; schoberg@medizin.uni-leipzig.de diana_leduc@eva.mpg.de.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Mar 15; Vol. 196 (6), pp. 2504-13. Date of Electronic Publication: 2016 Feb 05.
DOI:	10.4049/jimmunol.1501326
Abstrakt:	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. (Copyright © 2016 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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