Friday, 16 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)
Rabih Halwani, PhD
,
Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Asma Sultana, PhD
,
Prince Naif Center for Immunology Research, College of Medicine, King Saud University; Pnhrc, King Saud University, Riyadh, Saudi Arabia
Ahmed Bahammam
,
University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Saleh Al Muhsen, MD
,
Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Background Although IL-17-producing peripheral blood CD177+ neutrophils have recently been shown to increase in allergic asthmatic subjects, the mediators and mechanism regulating this increase in neutrophil derived IL-17 during asthma has not been properly investigated. IL-21, along with IL-6 and IL-23 cytokines, is important for the promotion of naïve CD4+ cells to differentiate toward the Th-17 cell lineage and the release of IL-17 cytokines. In this study, we explored the possibility that IL-21, IL-22 and IL-23 cytokines may activate peripheral blood neutrophils of asthmatic patients to release IL-17 cytokines and postulate that the response to stimulation could be different to that of neutrophils from non-asthmatic subjects.
Methods Peripheral blood neutrophils isolated from asthmatic as well as healthy controls were stimulated, or not, with IL-21, IL-23, and IL-6 cytokines and levels of gene as well as protein expression of IL-17 cytokines were determined using RT-PCR and flow cytometry, respectively. In addition, to investigate the mechanism of IL-21, IL-23, and IL-6 induced IL-17 release, level of Stat3 phosphorylation in neutrophils was determined following stimulation with these cytokines.
Results IL-21, IL-23, and IL-6 induced the production of IL-17 cytokines within peripheral blood neutrophils. Interestingly, the level of induced IL-17 cytokine were significantly higher in asthmatic compared to healthy control neutrophils. Stat3 phosphorylation was required for induction of IL-17 within neutrophils suggesting that a Stat3-RORgt pathway is involved and critical for regulating IL-21, 23, and 6 induced IL-17 production from neutrophils.
Conclusion Th-17 regulatory cytokines, IL-21, IL-23, and IL-6 induce the production of pro-inflammatory cytokine IL-17 from neutrophils in a much higher levels during asthma. This environment of high IL-17 levels could stimulate neutrophils to produce highly reactive oxygen radicals that would exacerbate the airway inflammatory response during asthma via their cytotoxic and tissue-destructive activity.
