Crosstalk between T cells and bronchial fibroblasts obtained from asthmatic subjects involves CD40L/alpha 5 beta 1 interaction.
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.
Loubaki
Lionel
L
Centre de recherche, Hôpital Laval, Institut universitaire de cardiologie et de pneumologie, Université Laval, Québec, Canada.
Semlali
Abdelhabib
A
Boisvert
Marc
M
Jacques
Eric
E
Plante
Sophie
S
Aoudjit
Fawzi
F
Mourad
Walid
W
Chakir
Jamila
J
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*
D019013:CD40 Antigens; D039081:Integrin alpha5beta1; D015850:Interleukin-6; D023201:CD40 Ligand