title: T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?
abstract: BACKGROUND
  A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.
  
  
  METHODS
  In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and negative (IFN⁻) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow cytometry and compared between IFN⁺, IFN⁻ patients and HCs.
  
  
  RESULTS
  Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ cells were observed in IFN⁺ patients compared with IFN⁻ patients and HCs. IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)-a factor strongly correlating with IFN type I - and IL-21 producing CCR6⁺ cells.
  
  
  CONCLUSIONS
  We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.
authors.forename: Zana
authors.initials: Z
authors.lastname: Brkic
authors.forename: Odilia B J
authors.initials: OB
authors.lastname: Corneth
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: van Helden-Meeuwsen
authors.forename: Radboud J E M
authors.initials: RJ
authors.lastname: Dolhain
authors.forename: Naomi I
authors.initials: NI
authors.lastname: Maria
authors.forename: Sandra M J
authors.initials: SM
authors.lastname: Paulissen
authors.forename: Nadine
authors.initials: N
authors.lastname: Davelaar
authors.forename: Jan Piet
authors.initials: JP
authors.lastname: van Hamburg
authors.forename: Paul L
authors.initials: PL
authors.lastname: van Daele
authors.forename: Virgil A
authors.initials: VA
authors.lastname: Dalm
authors.forename: P Martin
authors.initials: PM
authors.lastname: van Hagen
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Versnel
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D000328:Adult; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007370:Interferon Type I