Pathogenetic role of BATF in a murine model of allergic asthma (163.20)

Abstract

Abstract The transcription factor Basic leucine zipper transcription factor (BATF) is a member of the AP-1 family of transcription factors which upregulate gene expression of genes containing the TPA-DNA response element. However, BATF is thought to inhibit AP-1 activity. BATF has recently been described to be crucial for Th17 differentiation. BATF deficient mice lack this subset of T helper cells which is known to play a key role in inducing airway hyperresponsiveness in allergic asthma. In our study, we analyzed BATF deficient mice in a murine model of allergic asthma. We could show for the first time that BATF deficient mice show decreased lung Th2 cytokine production, reduced airway hyperresponsiveness, serum IgE and IgG1 levels after allergen challenge compared to wild-type littermates. The number of eosinophils was also diminished in the airways of BATF(-/-) compared to wild-type mice. We consider this phenotype to be primarily caused by the lack of IL-17A-producing Th17 cells. These results underline the importance of Th17 and the respective IL-17 cytokines for inducing and maintaining allergic diseases such as asthma. As there is a high similarity between human and murine BATF molecules, targeting this transcription factor could lead to the development of new treatment strategies against human asthma.