title: Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis.
abstract: BACKGROUND
  Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors.
  
  
  METHODS
  IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay.
  
  
  RESULTS
  TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30% ± 10% and 20% ± 7%, respectively; p < 0.05). In contrast, TGF-β promoted a significant increase in IL-13 mRNA levels and IL-13 synthesis by CD4(+) and CD8(+) T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production.
  
  
  CONCLUSIONS
  These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc.
authors.affiliation: INSERM U976, Pavillon Bazin, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75010, Paris, France. julie.baraut@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Baraut
authors.affiliation: Unité Clinique de Médecine Interne et Pathologie Vasculaire, UF 04, Hôpital Saint-Louis, AP-HP Assistance Publique des Hôpitaux de Paris, INSERM UMRS 1160, Paris, France. dominique.farge-bancel@aphp.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
authors.affiliation: INSERM U976, Pavillon Bazin, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75010, Paris, France. francette.jean-louis@inserm.fr.
authors.forename: Francette
authors.initials: F
authors.lastname: Jean-Louis
authors.affiliation: Université Claude Bernard Lyon I et CNRS UMR5534, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Villeurbanne, F-69622, France. ingrid.masse@univ-lyon1.fr.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Masse
authors.affiliation: INSERM U976, Pavillon Bazin, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75010, Paris, France. ivanmada79@yahoo.com.
authors.forename: Elena Ivan
authors.initials: EI
authors.lastname: Grigore
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. lucascma@usp.br.|Center for Cell-based Therapy, São Paulo Research Foundation (FAPESP), São Paulo, Brazil. lucascma@usp.br.
authors.forename: Lucas C M
authors.initials: LC
authors.lastname: Arruda
authors.affiliation: Université Claude Bernard Lyon I et CNRS UMR5534, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Villeurbanne, F-69622, France. jerome.lamartine@univ-lyon1.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lamartine
authors.affiliation: INSERM U957, Université de Nantes, 1 rue Gaston Veil, 44000, Nantes, France. franck.verrecchia@inserm.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Verrecchia
authors.affiliation: INSERM U976, Pavillon Bazin, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75010, Paris, France. laurence.michel@inserm.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis*; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis*; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050990:GATA3 Transcription Factor; D018793:Interleukin-13; D016212:Transforming Growth Factor beta