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IL-25 Causes Airway Hyper-Responsiveness of Human Precision Cut Lung Slices from Donors with Asthma.
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Jordan Heath, MD, Richard Kurten, PhD, Suzanne E House, James D Sikes, Megan Kurten, Stacie M. Jones, MD, Josh L. Kennedy, MD
Rationale: RV infection is associated with asthma exacerbations.  We sought to evaluate the role of IL-25 during RV infection, and whether IL-25 by itself was sufficient to cause AHR to carbachol in PCLS from donors with and without a history of asthma.

Methods:   PCLS from donors with and without history of asthma were prepared from cadaver transplant-grade lungs and cultured ex vivo.  Comparisons were made for innate immune responses between cohorts.  For contractility experiments, airway cross-sectional areas were measured before and after treatment with carbachol (0.1uM and 1uM). PCLS were treated with 10 uL/mL of IL-25, while others remained untreated for 24 hours. Post-exposure responses to IL-25 were measured, as above, before and after stimulation with carbachol, and comparisons were made between cohorts.

Results: IL-25 mRNA was enhanced secondary to viral infection.  RV39 and IL-25 caused AHR of PCLS, but only from donors with asthma (asthma: mean change from baseline (MCB) with:  RVC 9%;  IL-25 9%, no asthma:  RVC -14%; IL-25 -2.4%, untreated:  MCB -2.4%; p<0.05).  The IL-25 mRNA levels correlated with RV39 induced AHR in asthma donors(R= 0.64 for each; p<0.05).

Conclusions: RV39 induces mRNA expression of IL-25 in PCLS.  Further, both RV39 and IL-25 causes AHR in PCLS from asthma donors but not from controls.  This finding suggests that IL-25 is not the source of the AHR, but rather it may be necessary to trigger other cells (i.e., mast cells, ILC2 cells, T cells, or smooth muscle), leading to AHR.