title: Decreased expression of thymus-specific proteasome subunit β5t in Down syndrome patients.
abstract: OBJECTIVE
  The majority of patients with Down syndrome (DS), trisomy 21, have morphologically abnormal thymuses and present with intrinsic immunological abnormalities affecting mainly the cellular immune response. The aim of this study was to examine whether the expression of functionally important molecules is altered in thymic stromal cells in patients with DS.
  
  
  RESULTS
  We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as β5t, a thymoproteasome subunit, and cathepsins L and S. In patients with trisomy 13 and trisomy 18, the thymus was morphologically normal or showed only mild depletion of cortical thymocytes. In contrast, the thymus showed variable histological changes in patients with trisomy 21; six of 13 cases showed severe depletion of thymocytes accompanied by the disappearance of thymic lobular architecture. In such thymuses, spindle-shaped keratin-positive cells were densely distributed, and expression of β5t, but not of cathepsin L, was markedly decreased.
  
  
  CONCLUSIONS
  The present study suggests that abnormal thymic architecture and decreased expression of functionally important molecules in thymic stromal cells may be involved in immunological abnormalities in DS patients.
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.affiliation: Department of Diagnostic Pathology, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kiuchi
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.affiliation: Department of Diagnostic Pathology, KKR Sapporo Medical Centre, Sapporo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Physical Therapy, Faculty of Human Sciences, Hokkaido Bunkyo University, Eniwa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Diagnostic Pathology, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fukasawa
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D056668:Cathepsin L / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000201:enzymology; D002882:Chromosomes, Human, Pair 13 / Q000201:enzymology; D002887:Chromosomes, Human, Pair 18 / Q000201:enzymology; D004314:Down Syndrome / Q000201:enzymology* / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013194:Staining and Labeling; D017154:Stromal Cells / Q000473:pathology; D013950:Thymus Gland / Q000201:enzymology / Q000473:pathology; D014314:Trisomy; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D002403:Cathepsins; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S; C520308:PSMB11 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Down syndrome; proteasome subunit β5t; thymoproteasome; thymus; trisomy