title: The Prerequisites for Central Tolerance Induction against Citrullinated Proteins in the Mouse.
abstract: OBJECTIVE
  To assess the prerequisites for negative selection of peptidylcitrulline-specific T cells in the thymus. In detail, we here analyzed murine medullary thymic epithelial cells for the expression of peptidylarginine deiminases (PAD) and subsequent citrullination.
  
  
  METHODS
  Medullary thymic epithelial cells were sorted, their mRNA was isolated and the expression of Pad genes was analyzed by quantitative PCR. Citrullination was detected by Western Blot in lysates of sorted medullary thymic epithelial cells and histologically by immunofluorescence of thymic thin sections.
  
  
  RESULTS
  Pad2 and Pad4 are the main Pad isoforms expressed in mature medullary thymic epithelial cells of the mouse and their levels of expression are comparable to that of insulin (Ins2), another highly and promiscuously expressed protein in the thymus. Citrullination was detected in medullary thymic epithelial cells as shown by Western Blot and immunofluorescence.
  
  
  CONCLUSIONS
  Even though we here show that the murine thymus harbors the prerequisites for central tolerance to PAD and citrullinated peptides, it remains an open question whether the emergence of peptidylcitrulline-specific T cells and of autoantibodies recognizing citrullinated epitopes is caused by a failure of central or peripheral tolerance mechanisms.
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Robby
authors.initials: R
authors.lastname: Engelmann
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Andra
authors.initials: A
authors.lastname: Biemelt
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Cordshagen
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Johl
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuthning
authors.affiliation: Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Müller-Hilke
mesh_terms: D000818:Animals; D061167:Central Tolerance / Q000502:physiology*; D002956:Citrulline / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism*; D051379:Mice; D000080002:Protein-Arginine Deiminase Type 4; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
chemical_list: D002956:Citrulline; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; C552151:peptidylarginine deiminase 4, mouse