The leucine zipper transcription factor BATF induces IL-10 and IL-3 in allergic asthma (P6061)

Abstract

Abstract The transcription factor BATF is essentially involved in the differentiation of Th17 and follicular T helper cells. In B cells BATF influences the class-switch recombination of immunoglobulins. In an experimental model of allergic asthma we previously observed that BATF-/- mice do not develop asthma. We found that airway inflammation, hyperresponsiveness and eosinophilia were decreased, concomitant with lower serum IgE levels and reduced Th2 and Th17 cytokine secretion in the lung. Here we show an inhibition of IL-10 secretion in in vitro differentiated Th17 cells lacking BATF, while the expression of IRF4 mRNA was not altered. We confirmed a defect of IL-10 secretion in supernatants of total lung cells isolated from BATF-/- mice sensitized and challenged with OVA. Furthermore, IL-3, an important growth factor for the survival of eosinophils, basophils and mast cells, was also reduced in the supernatants of lung CD4+ T cells isolated from BATF-/- mice. Consistently, in BATF-/- mice treated with OVA, the number of lung mast cells expressing the IL-3 receptor α-chain was decreased. This defect was also confirmed in bone marrow derived mast cells. Taken together, BATF seems to play an important role not only in Th17 and Tfh differentiation but also in mast cell development. Therefore, local inhibition of BATF expression in the lung might be a feasible strategy for treating airway inflammation seen in allergic asthma.