title: Critical role of IL-21 in modulating TH17 and regulatory T cells in Behçet disease.
abstract: BACKGROUND
  Behçet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology.
  
  
  OBJECTIVE
  To determine the nature of T cells driving inflammatory lesions in BD.
  
  
  METHODS
  T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis.
  
  
  RESULTS
  We found a marked increase in T(H)17 cells and a decrease in the frequency of CD4(+) forkhead box P3(+) regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4(+) T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21- and IL-17A-producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4(+) T cells with IL-21 increased T(H)17 and T(H)1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the T(H)17 and Treg homeostasis in patients with BD.
  
  
  CONCLUSIONS
  We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting T(H)17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD.
authors: Laboratory I3 Immunology, Immunopathology, Immunotherapy, Groupe Hospitalier Pitié-Salpetrière, Université Pierre et Marie Curie, Paris, France.
authors: Guillaume
authors: G
authors: Geri
authors: Benjamin
authors: B
authors: Terrier
authors: Michelle
authors: M
authors: Rosenzwajg
authors: Bertrand
authors: B
authors: Wechsler
authors: Maxime
authors: M
authors: Touzot
authors: Danielle
authors: D
authors: Seilhean
authors: Tu-Anh
authors: TA
authors: Tran
authors: Bahram
authors: B
authors: Bodaghi
authors: Lucile
authors: L
authors: Musset
authors: Vassili
authors: V
authors: Soumelis
authors: David
authors: D
authors: Klatzmann
authors: Patrice
authors: P
authors: Cacoub
authors: David
authors: D
authors: Saadoun
mesh_terms: D000328:Adult; D000368:Aged; D001528:Behcet Syndrome / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21