title: RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy.
abstract: RhoB, a member of the Rho subfamily of small GTPases, mediates diverse cellular functions, including cytoskeletal organization, cell transformation and vesicle trafficking. The thymus undergoes progressive decline in its structure and function after puberty. We found that RhoB was expressed in thymic medullary epithelium. To investigate a role of RhoB in the regulation of thymic epithelial organization or thymocyte development, we analyzed the thymi of RhoB-deficient mice. RhoB-deficient mice were found to display earlier thymic atrophy. RhoB deficiency showed significant reductions in thymus weight and cellularity, beginning as early as 5 weeks of age. The enhanced expression of TGF-β receptor type II (TGFβRII) in thymic medullary epithelium was observed in RhoB-null mice. In addition, the expression of fibronectin, which is shown to be regulated by TGF-β signaling, was accordingly increased in the mutant thymic medulla. Since there is no age-related change of RhoB expression in the thymus, it is unlikely that RhoB in thymic epithelium directly contributes to age-related thymic involution. Nevertheless, our findings strongly support a physiological role of RhoB in regulation of thymus development and maintenance through the inhibition of TGF-β signaling in thymic medullary epithelium.
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Bravo-Nuevo
authors.forename: Rebekah
authors.initials: R
authors.lastname: O'Donnell
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosendahl
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
authors.forename: Laura E
authors.initials: LE
authors.lastname: Benjamin
authors.forename: Chikako
authors.initials: C
authors.lastname: Odaka
mesh_terms: D000818:Animals; D004848:Epithelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D020743:rhoB GTP-Binding Protein