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Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils

Saleh Al-Muhsen1, Severine Letuve2, Alejandro Vazquez-Tello1, Mary Angeline Pureza1, Hamdan Al-Jahdali13, Ahmed S Bahammam4, Qutayba Hamid5 and Rabih Halwani1*

Author Affiliations

1 Asthma Research Chair and Prince Naif Center for Immunology Research, Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia

2 Institut National de la Santé et de la Recherche Médicale (Inserm) U700 and Université Paris 7, Faculté de Médecine Denis Diderot, Site Bichat, Paris, France

3 King Saud University for health sciences, Riyadh, Saudi Arabia

4 Pulmonary Medicine Department, University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia

5 Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada

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Respiratory Research 2013, 14:34  doi:10.1186/1465-9921-14-34

Published: 13 March 2013



Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood.


In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines.


Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays.


The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release.


Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

Asthma; Eosinophils; Th17 cytokines; Pro-fibrotic cytokines; TGF-β; IL-11