Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function
Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C. Hoogsteden, Bart N. Lambrecht
Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C. Hoogsteden, Bart N. Lambrecht
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Research Article Immunology

Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function

Abstract

Inhalation of iloprost, a stable prostacyclin (PGI2) analog, is a well-accepted and safe treatment for pulmonary arterial hypertension. Although iloprost mainly acts as a vasodilator by binding to the I prostanoid (IP) receptor, recent evidence suggests that signaling via this receptor also has antiinflammatory effects through unclear mechanisms. Here we show in a murine model of asthma that iloprost inhalation suppressed the cardinal features of asthma when given during the priming or challenge phase. As a mechanism of action, iloprost interfered with the function of lung myeloid DCs, critical antigen-presenting cells of the airways. Iloprost treatment inhibited the maturation and migration of lung DCs to the mediastinal LNs, thereby abolishing the induction of an allergen-specific Th2 response in these nodes. The effect of iloprost was DC autonomous, as iloprost-treated DCs no longer induced Th2 differentiation from naive T cells or boosted effector cytokine production in primed Th2 cells. These data should pave the way for a clinical effectiveness study using inhaled iloprost for the treatment of asthma.

Authors

Marco Idzko, Hamida Hammad, Menno van Nimwegen, Mirjam Kool, Nanda Vos, Henk C. Hoogsteden, Bart N. Lambrecht

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Figure 2

Effect of iloprost treatment on distribution of DCs.

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Effect of iloprost treatment on distribution of DCs. Single-cell suspens...
Single-cell suspensions from MLNs were stained for DCs (A) or B and T cells (B) and analyzed by flow cytometry. Experiments were set up as in Figure 1. Labels indicate sensitization/treatment/challenge. Data (mean ± SEM) were calculated as absolute number of cells. **P < 0.01; ***P < 0.001. (C) Iloprost inhibited the maturation of lung DCs in vivo. A single-cell suspension was prepared from the lungs, and CD11c+MHCIIhi lung DCs were analyzed for their expression of CD40, CD80, CD83, and CD86. Data from 1 representative experiment of 3 is shown.