title: Rac1 deletion causes thymic atrophy.
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.
authors.affiliation: Centre for Respiratory Research, University College London, London, United Kingdom.
authors.forename: Lukas
authors.initials: L
authors.lastname: Hunziker
authors.forename: Salvador Aznar
authors.initials: SA
authors.lastname: Benitah
authors.forename: Salvador
authors.initials: S
authors.lastname: Aznar Benitah
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Braun
authors.forename: Kim
authors.initials: K
authors.lastname: Jensen
authors.forename: Katrina
authors.initials: K
authors.lastname: McNulty
authors.forename: Colin
authors.initials: C
authors.lastname: Butler
authors.forename: Elspeth
authors.initials: E
authors.lastname: Potton
authors.forename: Emma
authors.initials: E
authors.lastname: Nye
authors.forename: Richard
authors.initials: R
authors.lastname: Boyd
authors.forename: Geoff
authors.initials: G
authors.lastname: Laurent
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
authors.forename: Nick A
authors.initials: NA
authors.lastname: Wright
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
authors.forename: Sam M
authors.initials: SM
authors.lastname: Janes
mesh_terms: D000818:Animals; D001284:Atrophy; D049109:Cell Proliferation; D003433:Crosses, Genetic; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006579:Heterozygote; D006706:Homeostasis; D007668:Kidney / Q000196:embryology; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013950:Thymus Gland / Q000196:embryology / Q000473:pathology*; D013997:Time Factors; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D049452:Green Fluorescent Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein