title: Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis.
abstract: OBJECTIVE
  To examine the expression and regulation of interleukin-21 (IL-21) and IL-21 receptor (IL-21R) in patients with systemic sclerosis (SSc; scleroderma).
  
  
  METHODS
  Skin biopsy specimens were obtained from 23 patients with SSc and 15 healthy controls. IL-21/IL-21R messenger RNA (mRNA) was quantified using real-time polymerase chain reaction (PCR). The expression pattern of IL-21/IL-21R was analyzed by in situ hybridization and Western blotting. Stimulation experiments were performed with cultured dermal fibroblasts from patients with SSc and healthy controls as well as with keratinocytes, using IL-1beta, platelet-derived growth factor BB, monocyte chemoattractant protein 1, transforming growth factor beta, and IL-21. The SCID-hu skin mouse model was used for in vivo experiments.
  
  
  RESULTS
  IL-21R mRNA was detected in all biopsy specimens from patients with SSc and controls, with a 4.7-fold increase observed in SSc samples. In situ hybridization and immunohistochemical analysis showed an up-regulation of IL-21R in samples of epidermis from SSc patients, whereas no signal was detected in skin specimens from healthy controls. These results were confirmed in vitro, in that cultured keratinocytes expressed significant levels of IL-21R, whereas no signal was observed in fibroblasts. Interestingly, mRNA for IL-21 could not be detected by real-time PCR and in situ hybridization. Various concentrations of key cytokines in the pathogenesis of SSc did not stimulate the expression of IL-21R mRNA in cultured keratinocytes and dermal fibroblasts. In the SCID mouse transplantation model, the overexpression of IL-21R mRNA in SSc keratinocytes remained unchanged after transplantation.
  
  
  CONCLUSIONS
  The up-regulation of IL-21R in keratinocytes indicates that, similar to fibroblasts and endothelial cells, the expression pattern is altered in SSc. Moreover, the expression of IL-21R appears to be independent of key cytokines that are operant in SSc.
authors.affiliation: University Hospital Zurich, Zurich, Switzerland.
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Astrid
authors.initials: A
authors.lastname: Jüngel
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
authors.forename: Beat A
authors.initials: BA
authors.lastname: Michel
authors.forename: Renate E
authors.initials: RE
authors.lastname: Gay
authors.forename: Haiko
authors.initials: H
authors.lastname: Sprott
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Meike
authors.initials: M
authors.lastname: Chilla
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Kalden
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Hanns M
authors.initials: HM
authors.lastname: Lorenz
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D023421:Models, Animal; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053655:Receptors, Interleukin-21; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; C508117:IL21R protein, human; C508118:Il21r protein, mouse; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D042461:Vascular Endothelial Growth Factor A; D000098546:Interleukin-21