Distinct roles of FOXA2 and FOXA3 in allergic airway disease

Allergen challenge induced mucus metaplasia modify the expression of two transcription factors belonging to the FOXA family: FOXA2 and FOXA3. Foxa2 expression is decreased during allergic airway disease whereas, Foxa3 expression is increased by allergen. Therefore, we asked whether persistent expression of Foxa2 prevents mucus and whether absence of Foxa3 affects mucus or other features asociated with allergic airway disease. We analyzed the effects of these changes in FOXA transcription factor expression using Foxa2 transgenic mice and Foxa3-/- mice. We found that persistent expression of FOXA2 reduced mucus but the absence of FOXA3 had no effect on mucus production induced by allergen challenge. However, the absence of FOXA3 decreased airway hyperreactivity and increased IgE production and eosinophilic inflammation but none of these features were affected by persistent expression of FOXA2. These results indicate that FOXA3 has functions distinct from those of FOXA2 in the allergic response. Keywords: gene expression comparison between Foxa3-/- and littermate control mice both challenged with OVA DNA miocroarrays were used to analyze lung mRNA expression of Foxa3 KO and littermate control mice challenged with saline or OVA. The experiment incorporated a 1 color design and used Agilent arrays that contained roughly 44,000 60mer probes that provide complete coverage of the mouse genome. 11 arrays were hybridized and represent 3 lung samples for groups WT saline, WT OVA and KO OVA. There are 2 lung samples for the KO saline group.