Differential effect of fluticasone on Poly(I:C) induced TSLP secretion by bronchial epithelial cells from asthmatic children

Abstract

Acute exacerbations of asthma in children are mainly triggered by virus. Inhaled glucocorticoids are the main treatment but their role to prevent virus induced exacerbations is not established. TSLP, an epithelial cytokine, promote Th2 activation. However, TSLP has multifaceted functions ranging from tolerance to activation of immune cells due to presence of two variants: a long form (lfTSLP) and a short form (sfTSLP).

We aim to explore the role of Fluticasone propionate (FP) on TSLP secretion and isoforms expression in an ex vivo model of asthma exacerbation using bronchial epithelial cell (BEC) obtained from children.

BEC from asthmatic (n =7) and non asthmatic children (n=8) were cultured on air-liquid interface. We challenged BEC with poly(I:C) to mimic viral exacerbation, after pretreatment or not with FP during 4 days. TSLP secretion was measured in basolateral secretion and TSLP variants mRNA expression was studied.

Spontaneous TSLP release is similar in asthma and control and sfTSLP is predominantly expressed compared to lfTSLP. Poly(I:C) significantly increases TSLP release in both group of children. In BEC from asthmatic children, FP has no effect on poly(I:C)-induced TSLP secretion compared to control in which FP significantly decreases this release. Study of TSLP isoform shows that poly(I:C) increases lfTSLP but has no effect on sfTSLP. However, FP seems to increase sfTSLP and decrease lfTSLP only in non asthmatic children.

These results show that in asthma, FP has a different effect on the virus-induced TSLP secretion and on the regulation of TSLP isoforms compared to controls. The long-term use of FP may limit the adaptive immunity in asthma.