Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules.

Autor:	Reinicke AT; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Raczkowski F; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Mühlig M; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schmucker P; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Lischke T; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Reichelt J; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Schneider E; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Zielinski S; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Sachs M; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Jurack E; Institute of Molecular Medicine and Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany., Tolosa E; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Kurts C; Institute of Molecular Medicine and Experimental Immunology, University Clinic of Bonn, 53127 Bonn, Germany., Mittrücker HW; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; and., Meyer-Schwesinger C; Institute for Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; c.meyer-schwesinger@uke.uni-hamburg.de.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Oct 01; Vol. 203 (7), pp. 1730-1742. Date of Electronic Publication: 2019 Sep 06.
DOI:	10.4049/jimmunol.1801133
Abstrakt:	The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1) is required for the maintenance of axonal integrity in neurons and is thought to regulate the intracellular pool of ubiquitin in the brain. In this study, we show that UCH-L1 has an immunological function in dendritic cell (DC) Ag cross-presentation. UCH-L1 is expressed in mouse kidney, spleen, and bone marrow-derived DCs, and its expression and activity are regulated by the immune stimuli LPS and IFN-γ. UCH-L1-deficient mice have significantly reduced ability to cross-prime CD8 T cells in vivo and in vitro because of a reduced ability of DCs to generate MHC class I (MHC I) peptide complexes for cross-presented Ags. Mechanistically, Ag uptake by phagocytosis and receptor-mediated endocytosis as well as phagosome maturation are unaffected by loss of UCH-L1 in DCs. Rather, MHC I recycling is reduced by loss of UCH-L1, which affects the colocalization of intracellular MHC I with late endosomal/lysosomal compartments necessary for cross-presentation of Ag. These results demonstrate a hitherto unrecognized role of the deubiquitinating enzyme UCH-L1 in DC Ag processing. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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