title: Crosstalk between T cells and bronchial fibroblasts obtained from asthmatic subjects involves CD40L/alpha 5 beta 1 interaction.
abstract: BACKGROUND
  Allergic asthma is characterized by infiltration of inflammatory cells into the airways. T cell-derived cytokines regulate both airway inflammation and remodelling. In the human airways, T cell-fibroblast interactions may have a role in regulating inflammation and remodelling.
  
  
  OBJECTIVE
  To evaluate the effect of bronchial fibroblast-T cell interaction on profibrogenic cytokine release and determine the nature of the molecules involved in this interaction.
  
  
  METHODS
  Human bronchial fibroblasts obtained from healthy and asthmatic donors were co-cultured with purified T cells derived from peripheral blood of the same subjects. IL-6 mRNA and protein levels were measured by real time PCR and ELISA. CD40, CD40L and alpha 5 beta 1 were evaluated by flow cytometry. Bronchial fibroblasts were stimulated with rsCD40L. Neutralisation was performed using neutralizing antibodies anti-CD40L and anti-alpha 5.
  
  
  RESULTS
  Contact of T cells with bronchial fibroblasts up-regulated IL-6 at both gene and protein levels. This effect was significantly higher in fibroblasts from asthmatics than those from controls. Blocking CD40L and alpha 5 beta 1 integrin showed a significant inhibition of IL-6 expression in asthmatics but not in healthy controls. Stimulation of fibroblasts with recombinant soluble CD40L up-regulated IL-6 production in asthmatics but not in controls. Adhesion to fibronectin, a alpha 5 beta 1 integrin ligand, is increased in fibroblasts from asthmatics compared to fibroblasts from controls.
  
  
  CONCLUSIONS
  These results showed that interaction of bronchial fibroblasts with T cells increases the production of profibrogenic cytokine IL-6. In asthmatic condition this interaction involves CD40L/alpha 5 beta 1. These results suggest that T cells and structural cells crosstalk in asthma may maintain local mucosal inflammation.
authors.affiliation: Centre de recherche, Hôpital Laval, Institut universitaire de cardiologie et de pneumologie, Université Laval, Québec, Canada.
authors.forename: Lionel
authors.initials: L
authors.lastname: Loubaki
authors.forename: Abdelhabib
authors.initials: A
authors.lastname: Semlali
authors.forename: Marc
authors.initials: M
authors.lastname: Boisvert
authors.forename: Eric
authors.initials: E
authors.lastname: Jacques
authors.forename: Sophie
authors.initials: S
authors.lastname: Plante
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000166:cytology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D019013:CD40 Antigens; D039081:Integrin alpha5beta1; D015850:Interleukin-6; D023201:CD40 Ligand