Crosstalk between T cells and bronchial fibroblasts obtained from asthmatic subjects involves CD40L/alpha 5 beta 1 interaction

• Published in: Molecular immunology Vol. 47; no. 11-12; p. 2112
• Main Authors: Loubaki, Lionel, Semlali, Abdelhabib, Boisvert, Marc, Jacques, Eric, Plante, Sophie, Aoudjit, Fawzi, Mourad, Walid, Chakir, Jamila
• Format: Journal Article
• Language: English
• Published: England 01.07.2010
• Subjects: Adult; Asthma - immunology; Bronchi - cytology; CD40 Antigens - physiology; CD40 Ligand - physiology; Cell Adhesion; Cell Communication; Cells, Cultured; Fibroblasts - physiology; Humans; Integrin alpha5beta1 - physiology; Interleukin-6 - biosynthesis; T-Lymphocytes - physiology
• ISSN: 1872-9142; 1872-9142
• DOI: 10.1016/j.molimm.2010.03.011

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. 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. 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. 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. 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.