%0 Journal Article %A Sofia Tousa %A Maria Semitekolou %A Ioanna Christopoulou %A Konstantinos Samitas %A Giannis Paraskevopoulos %A Catherine Hawrylowicz %A Mina Gaga %A Georgina Xanthou %T Critical immunoregulatory role for activin-A in human allergic asthma %D 2011 %J European Respiratory Journal %P p4094 %V 38 %N Suppl 55 %X Our studies have revealed that activin-A, a cytokine increased in the sera and lungs of asthmatics, is a critical controller of experimental asthma as it suppresses allergic responses and protects against airway hyperresponsiveness and linked disease in mice. Still, the role of activin-A in human asthma remains elusive. Here, we investigated the effects of activin-A in the suppression of allergic responses of atopics and asthmatics. Peripheral blood (PB) was obtained from atopics and mild/moderate or severe asthmatics (n=12/group). Bronchoalveolar lavage (BAL) was obtained from severe asthmatics (n=5). The effects of recombinant activin-A or control on allergen-specific CD4+ T cell proliferation and cytokine release were investigated during stimulation with allergen ex vivo. Activin-A's role in the generation of suppressive human regulatory T cells (Tregs) was studied. Our findings reveal that activin-A significantly suppresses allergen-driven CD4+ T cell proliferation and IL-5, IL-13, IL-17, IFN-γ, IL-10 release in atopics and asthmatics. Activin-A suppresses BAL mononuclear cell responses of severe asthmatics. Importantly, activin-A enhances dexamethasone-induced suppression of allergic Th2 responses of severe, treatment refractory, asthmatics. Activin-A mediated suppression is associated with the generation of human CD4+Foxp3+ Tregs that completely inhibit allergic Th2 responses. Our results uncover activin-A as a novel protective cytokine that controls human asthma. Our findings have important clinical implications for the use of activin-A, or activin-A-induced human Tregs, as novel immunotherapies for asthma. %U