Activin A is an acute allergen-responsive cytokine and provides a link to TGF-[beta]-mediated airway remodeling in asthma

Background Allergic asthma typically shows activated, allergen-specific CD4+T cells in the early phase and airway remodeling in the late phase of the disease. Although TGF-β plays a crucial role in airway remodeling, it is only marginally induced in CD4+T cells in the early allergen-dependent activation of the immune system. Objective To elucidate the transition between early- and late-phase events, we investigated the role of activin A, a close family member of TGF-β. Methods Activin A and TGF-β1levels were measured systemically in the serum and in CD4+T cells of asthmatic patients, as well as locally in the lung. Results Activin A serum levels were increased in patients with severe asthma compared with levels in patients with moderate asthma and healthy control subjects, whereas all patients showed significantly increased TGF-β1serum levels independent of disease severity. In T cells only patients with moderate asthma showed increased activin A mRNA expression, whereas TGF-β1expression was equal to that seen in healthy subjects. Accordingly, ovalbumin sensitization in a mouse model of allergic asthma could induce activin A mRNA expression, but not TGF-β1expression, in the lung. Immunohistochemistry of mice and human specimens revealed an abundant expression of activin A by infiltrating lymphocytes and structural cells of the lung. Although TGF-β1more potently enhanced proliferation and Smad 2/3-dependent reporter genes in fibroblasts, activin A was capable of inducing TGF-β1and vice versa. Conclusion Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-β1-mediated airway remodeling in asthma.