title: Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients.
  
  
  METHODS
  Peripheral blood of 34 SLE patients and 18 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore (Ca-Io). Percentages of IL-21- and IL-17A expressing T-cells were analysed by flow cytometry. The expression levels of the transcription factors B-cell lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-γt) were assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21 receptor (IL-21R) expression on B- and T-cells of patients and HC was analyzed.
  
  
  RESULTS
  Significantly increased percentages of IL-21 expressing CD4+ T-cells and CD8+ T-cells were found in SLE patients as compared to HC. The percentages of IL-21+ CD4+ T-cells and CD8+ T-cells correlated significantly with the percentages of IL-17A+ CD4+ T-cells and CD8+ T-cells, respectively. The relative expression of BCL-6 and ROR-γt did not differ between SLE patients and HC. IL-21R expression occurred mainly on B-cells and was not different comparing SLE patients and HC.
  
  
  CONCLUSIONS
  This study demonstrates an increased proportion of IL-21+ T-cells in SLE patients correlating with the proportion of IL-17+ T-cells. This suggests a pivotal role of IL-21 in the pathogenesis of SLE.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. Sebastian.Dolff@uk-essen.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.forename: Berber
authors.initials: B
authors.lastname: Doornbos-van der Meer
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Limburg
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21