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Rac1 Deletion Causes Thymic Atrophy

Hunziker, L; Benitah, SA; Braun, KM; Jensen, K; McNulty, K; Butler, C; Potton, E; ... Janes, SM; + view all (2011) Rac1 Deletion Causes Thymic Atrophy. PLOS ONE , 6 (4) , Article e19292. 10.1371/journal.pone.0019292. Green open access

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Abstract

The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

Type: Article
Title: Rac1 Deletion Causes Thymic Atrophy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0019292
Publisher version: http://dx.doi.org/10.1371/journal.pone.0019292
Language: English
Additional information: © 2011 Hunziker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. SAB, KMB, NW, and FMW were supported by Cancer Research UK (http://www.cancerresearchuk.org). LH was supported by the following grants: Swiss national foundation PBBSB-108681, the Freiwillige Akademische Gesellschaft and the Margarete und Walter Lichtenstein Stiftung. KMB was supported by EuroStemCell (http://www.eurostemcell.org/). KM is an MRC Clinical Training Fellow (http://www.mrc.ac.uk/index.htm). SMJ is a Wellcome Senior Fellow in Clinical Science (WT091730MA)(http://www.wellcome.ac.uk/). This work was partially undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: EPITHELIAL PROGENITOR CELLS, STEM-CELLS, MEDULLARY EPITHELIUM, POSITIVE SELECTION, EPIDERMAL DELETION, MYC ACTIVATION, DIFFERENTIATION, MOUSE, EXPRESSION, PROLIFERATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1307833
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