title: The deubiquitinating enzyme CYLD regulates the differentiation and maturation of thymic medullary epithelial cells.
abstract: The cross talk between thymocytes and the thymic epithelium is critical for T-cell development and the establishment of central tolerance. Medullary thymic epithelial cells (mTECs) are located in the thymic medulla and mediate the elimination of self-reactive thymocytes, thereby preventing the onset of autoimmunity. Previous studies identified the deubiquitinating enzyme CYLD as a critical regulator of T-cell development by activating proximal T-cell receptor signaling during the transition of double-positive to single-positive thymocytes. Here we evaluated the impact of the naturally occurring short-splice variant of the cyld gene (sCYLD) on the development and maturation of mTECs. We found that thymi of CYLD(ex7/8) mice, solely expressing sCYLD, displayed a reduced number of mature mTECs caused by a developmental block during the transition of immature to mature mTECs. Further, we could demonstrate an impaired negative selection of thymocytes in these mice. Our data demonstrate that inefficient negative selection in the thymus of CYLD(ex7/8) mice result from a defect in mTEC maturation.
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Reissig
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Hövelmeyer
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Yilang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Immunology Group, Leibniz-Institute for Age Research-Fritz-Lipmann-Institute (FLI), Jena, Germany.
authors.forename: Debra
authors.initials: D
authors.lastname: Weih
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Nikolaev
authors.affiliation: Immunology Group, Leibniz-Institute for Age Research-Fritz-Lipmann-Institute (FLI), Jena, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Riemann
authors.affiliation: Immunology Group, Leibniz-Institute for Age Research-Fritz-Lipmann-Institute (FLI), Jena, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000074749:Deubiquitinating Enzyme CYLD; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases