title: IFN-α induces IL-10 production and tilt the balance between Th1 and Th17 in Behçet disease.
abstract: OBJECTIVE
  Interferon alpha (IFN-α) is an effective treatment for patients with active Behçet disease (BD). Besides its antiviral property, IFN-α is a cytokine with pleiotropic effects that can generate an anti-inflammatory environment or inhibit specific inflammatory T cells such as Th1 and Th17 cells. However, it is not known, in BD patients, whether IFN-α inhibits pro inflammatory T cells, or induces anti-inflammatory properties in T cells.
  
  
  METHODS
  Total memory CD45RO(+) T cells purified from peripheral blood mononuclear cells (PBMCs) obtained from patients with active BD (N=5), systemic lupus erythematosus (SLE, N=5) or healthy control (HC, N=6) were cultured in vitro with or without IFN-α. Levels of IFN-γ, IL-17, IL-10, IL-6, and TNF-α in the supernatants were analyzed by ELISA, Cytometric Beads Array (CBA) or intracellular cytokine staining. We analyzed the production of IL-10 on the memory subsets Th1 (mTh1), Th2 (mTh2) and Th17 (mTh17).
  
  
  RESULTS
  IFN-α significantly increased IFN-γ level in memory CD4(+) T cells in BD patients and HC, but not SLE patients. IL17 was not inhibited by IFN-α in BD or in SLE patients. However, IFN-α modulated the pro- and anti-inflammatory cytokines secreted by T cells as it increased the IL-10/IL-6 ratio in BD and HC, but not SLE patients. We further demonstrated that IFN-α increased IL-10 secretion in each memory subset mTh1, mTh2 and mTh17.
  
  
  CONCLUSIONS
  In BD, IFN-α promotes a regulatory Th1 response through IL-10 secretion. This effect may explain the efficacy of IFN-α in inflammatory disease.
authors.affiliation: INSERM U932, 26 Rue d'Ulm, 75005 Paris, France; Institut Curie, Section Recherche, 26 Rue d'Ulm, 75005 Paris, France; Laboratoire d'Immunologie Clinique, Institut Curie, 26 Rue d'Ulm, 75005 Paris, France. Electronic address: mtouzot@gmail.com.
authors.forename: Maxime
authors.initials: M
authors.lastname: Touzot
authors.affiliation: Département de Médecine Interne et d'Immunologie Clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, Boulevard de l'Hôpital, Paris 75013, France; Centre National de Référence Maladies Systémiques et Autoimmunes Rares, DHU Inflammation, Immunopathologie, Biothérapie, Université Paris VI-Pierre et Marie Curie, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.affiliation: Service d'Ophtalmologie, Groupe Hospitalier Pitié-Salpêtrière, 84, Boulevard de l'Hôpital, Paris 75013, France.
authors.forename: Bahram
authors.initials: B
authors.lastname: Bodaghi
authors.affiliation: INSERM U932, 26 Rue d'Ulm, 75005 Paris, France; Institut Curie, Section Recherche, 26 Rue d'Ulm, 75005 Paris, France; Laboratoire d'Immunologie Clinique, Institut Curie, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
authors.affiliation: Département de Médecine Interne et d'Immunologie Clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, Boulevard de l'Hôpital, Paris 75013, France; Centre National de Référence Maladies Systémiques et Autoimmunes Rares, DHU Inflammation, Immunopathologie, Biothérapie, Université Paris VI-Pierre et Marie Curie, Paris, France. Electronic address: david.saadoun@pls.aphp.fr.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
mesh_terms: D001528:Behcet Syndrome / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; D016753:Interleukin-10
keywords: Behçet's disease; IL-10; Interferon; Systemic lupus erythematosus; T helper cells