• Damian Tworek, Steven G Smith, Brittany M Salter, Adrian J Baatjes, Tara Scime, Rick Watson, Caitlin Obminski, Gail M Gauvreau, and Paul M O'Byrne.
• 1 Firestone Institute of Respiratory Health and the Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; and.
• Am. J. Respir. Crit. Care Med. 2016 May 1; 193 (9): 957-64.

RationaleIL-25 is an epithelial-derived cytokine, whose effects are mediated by the IL-25 receptor (IL-17RB), and that has been implicated in the pathogenesis of allergic disease and airway viral responses. Airway myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells. pDCs may play a protective role in asthma and are key players in the innate immune response through recognition of microbial products via Toll-like receptors (TLRs). The effects of inhaled allergens on the expression of IL-17RB by mDCs and pDCs, and the effects of IL-25 on pDCs, are unknown.ObjectivesTo evaluate allergen-induced changes in IL-17RB expression by mDCs and pDCs and to investigate the effects of IL-25 on pDCs.MethodsPatients with mild atopic asthma (n = 13) were challenged with inhaled allergen. Blood and sputum DCs were enumerated and IL-17RB expression was determined by flow cytometry before and 7 and 24 hours after allergen challenge. The effects of IL-25 on pDCs in vitro were also assessed.Measurements And Main ResultsInhaled allergen significantly increased mDC and pDC numbers in sputum but not in blood. The percentage of IL-17RB(+) mDCs and pDCs was significantly increased in blood and sputum 24 hours after challenge. IL-25 up-regulated TLR9 expression by pDCs and orchestrated the responses to TLR9 ligation.ConclusionsIL-17RB is up-regulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.

32 keywords...

hide…