Maxime Touzot1, Patrice Cacoub2, Bahram Bodaghi3, Vassili Soumelis4, David Saadoun5. 1. 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. 2. 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. 3. Service d'Ophtalmologie, Groupe Hospitalier Pitié-Salpêtrière, 84, Boulevard de l'Hôpital, Paris 75013, France. 4. 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. 5. 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.
Abstract
BACKGROUND AND AIMS: 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.
BACKGROUND AND AIMS: 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 SLEpatients. IL17 was not inhibited by IFN-α in BD or in SLEpatients. 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 SLEpatients. 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: Giuseppe Lopalco; Orso Maria Lucherini; Antonio Vitale; Rosaria Talarico; Antonio Lopalco; Mauro Galeazzi; Giovanni Lapadula; Luca Cantarini; Florenzo Iannone Journal: Medicine (Baltimore) Date: 2015-10 Impact factor: 1.817