IL-33 and IL-13 Receptors Are Upregulated in Precision Cut Lung Slices from Donors with Asthma during RV39 Infection.

Rationale: IL-25, TSLP, and IL-13 are increased in precision cut lung slices (PCLS) from donors with asthma infected with rhinovirus (RV). However, whether the quantitative increase in cytokine levels correlates to upregulated receptor expression is unknown.   We hypothesized receptor expression for IL-25, TSLP, and IL-13 would be enhanced in PCLS from asthma donors infected with RV39 compared to controls. 

Methods: We used precision cut lung slices (PCLS) from donors with (n=5) and without asthma (n=16) and compared rhinovirus infected (RV39) samples from both cohorts at 0, 2, and 48 hours for expression of TSLPR, IL-13Ra, ST2, ST2L, and IL25R.  Expression was normalized to beta-actin and uninfected tissue from the same lung and the same time point. Comparisons were made using Mann-Whitney.

Results: ST2 and IL-13Ra were increased in PCLS from asthma donors after infection at 48 hours compared to control tissue (ST2 median 3.64 asthma; median -0.92 control; p<005; IL-13Ra median 5.09 asthma; median -1.040 control; p<0.05).  TSLPR and IL-25R trended towards higher expression in tissue from asthma donors (p=0.08, p=0.06, respectively).  Further, in comparisons of asthma donors infected with RV between 2 and 48 hours, ST2, IL-13Ra, and TSLPR were significantly increased (p<0.05) and were not in controls.

Conclusions: Innate allergic inflammatory cytokines and their respective receptors are up-regulated during RV39 infection in PCLS from asthma donors, suggesting that these cytokines are active.  Infection with RV39 in PCLS from asthma donors leads to increased receptor expression over time, suggesting that the infection plays a role in the regulation of the receptors.