title: New role for the (pro)renin receptor in T-cell development.
abstract: The (pro)renin receptor (PRR) was originally thought to be important for regulating blood pressure via the renin-angiotensin system. However, it is now emerging that PRR has instead a generic role in cellular development. Here, we have specifically deleted PRR from T cells. T-cell-specific PRR-knockout mice had a significant decrease in thymic cellularity, corresponding with a 100-fold decrease in the number of CD4(+) and CD8(+) thymocytes, and a large increase in double-negative (DN) precursors. Gene expression analysis on sorted DN3 thymocytes indicated that PRR-deficient thymocytes have perturbations in key cellular pathways essential at the DN3 stage, including transcription and translation. Further characterization of DN T-cell progenitors leads us to propose that PRR deletion affects thymocyte survival and development at multiple stages; from DN3 through to DN4, double-positive, and single-positive CD4 and CD8. Our study thus identifies a new role for PRR in T-cell development.
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Max-Delbruck Center for Molecular Medicine, Berlin, Germany;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Geisberger
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Max-Delbruck Center for Molecular Medicine, Berlin, Germany;
authors.forename: Ulrike
authors.initials: U
authors.lastname: Maschke
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Max-Delbruck Center for Molecular Medicine, Berlin, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Gebhardt
authors.affiliation: Faculty of Medicine, Dresden University of Technology, Dresden, Germany;
authors.forename: Markus
authors.initials: M
authors.lastname: Kleinewietfeld
authors.affiliation: Department of Neurology, University of Erlangen, Erlangen, Germany;
authors.forename: Arndt
authors.initials: A
authors.lastname: Manzel
authors.affiliation: Department of Neurology, University of Erlangen, Erlangen, Germany;
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia;
authors.forename: Ann
authors.initials: A
authors.lastname: Chidgey
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; HELIOS-Klinikum Berlin, Berlin, Germany;
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: INSERM and College de France, Center for Interdisciplinary Research in Biology, Paris, France;
authors.forename: Genevieve
authors.initials: G
authors.lastname: Nguyen
authors.affiliation: Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Daumke
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Max-Delbruck Center for Molecular Medicine, Berlin, Germany;
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
authors.affiliation: Department of Immunology, Monash University, Prahran, Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wright
authors.affiliation: Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Max-Delbruck Center for Molecular Medicine, Berlin, Germany;
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Binger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; C045073:Cre recombinase; D019426:Integrases; D000093342:Prorenin Receptor