Interleukin-25 Induces Pulmonary Arterial Remodeling via Natural Killer T Cell-Dependent Mechanisms

Background: Recent studies have shown that prolonged Th2-type immune inflammation in the lung induces pulmonary arterial remodeling, in part through the induction of resistin-like molecule alpha (RELM alpha) expression. However, the role of interleukin-25 (IL-25; which promotes this inflammation) in the development of the pulmonary arterial remodeling remains unknown. Methods: Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged with OVA inhalation 3 times a week for 3 weeks. The effects of neutralizing antiIL- 25 antibody on OVA-induced pulmonary arterial remodeling and RELMa expression in the lung were examined. The pulmonary arterial remodeling and RELMa expression in the lung were examined in lung-specific IL-25 transgenic mice (CC10 IL-25 mice) and CC10 IL-25 mice in a natural killer T (NKT) cell-deficient background (CC10 IL-25 NKT-/- mice). Results: Repeated OVA inhalation induced pulmonary arterial wall thickening and the expression of IL-25 and RELMa mRNA in the lung in OVA-sensitized mice. Injection of neutralizing anti-IL-25 antibody inhibited OVA-induced pulmonary arterial wall thickening and RELMa expression in the lung. CC10 IL-25 mice, but not CC10 IL-25 NKT-/- mice, spontaneously developed pulmonary arterial wall thickening and RELMa expression in the lung at 6 months of age. Conclusions: Prolonged expression of IL-25 in the lung induces pulmonary arterial wall thickening by NKT cell-dependent mechanisms. Copyright (C) 2013 S. Karger AG, Basel