The deletion of Bambi attenuates experimental asthma in mice

Allergic bronchial asthma is a chronic inflammatory lung disease. Transforming growth factor beta (TGF-b) is an important factor for the initiation and development of allergic asthma by controlling the differentiation of various T cell subtypes and by the regulation of structural changes. Bambi (Bone Morphogenetic Protein and Activin Membrane-bound Inhibitor) was described to act as TGF-b type I pseudoreceptor. This study aimed at exploring the role of Bambi in the development of human and murine asthma. Human naïve CD4+ T cells were isolated by MACS, and differentiated towards regulatory T cells (Tregs). Tregs were analyzed by FACS and qPCR for expression of Bambi. Wildtype C57Bl/6 and Bambi KO mice were sensitized with ovalbumin (OVA) adsorbed to Alum and challenged with an OVA aerosol on three consecutive days. Lung function, airway inflammation, cytokine expression, and OVA-specific antibodies were assessed. Human Tregs showed strong induction of Bambi expression, corroborating its potential role in asthma development. Bambi KO mice showed significantly reduced airway hyperresponsiveness. Lung inflammation was attenuated, in particular the number of eosinophils was reduced in broncho-alveolar lavage fluid (BALF) of Bambi KO mice. Moreover, typical T helper type 2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 as well as the pro-inflammatory IL-6 were diminished in Bambi KO mice compared to wildtype mice. There were no differences with regard to TGF-b levels in BALF and OVA-specific IgG titers in serum. The deletion of Bambi interferes with the development of experimental asthma. In vitro data suggest that this effect is mediated by a potential regulatory role for Bambi in TGF-b driven Treg differentiation.