Activin-A: A New Piece in the Puzzle of Tolerance in Asthma

Abstract

Activin-A is a member of the TGF-β superfamily, initially identified as an inducer of follicle-stimulating hormone secretion. Activin-A is highly conserved in evolution and modulates fundamental biological processes such as embryonic development, stem cell maintenance and differentiation, hematopoiesis, cell proliferation and fibrosis. Emerging data support a role for activin-A as a true cytokine that can exert both pro- and anti-inflammatory activities depending on the cell type, the cytokine micromilieu and the context of the immune response. Interestingly, a large body of evidence suggests that activin-A is increased in experimental models of allergic airway inflammation and in the airways of individuals with asthma. Importantly, in vivo functional studies have uncovered a key role for activin-A in the suppression of allergen-driven T helper (Th) type 2 cell responses and the amelioration of experimental asthma manifestations through the induction of strongly suppressive IL-10-producing regulatory T cells (Tregs). Of clinical relevance, activin-A and its signaling components are activated in the airways of individuals and asthmatics, pointing to a role for activin-A in the regulation of human allergic responses. Here, we provide an overview of the biology of activin-A and review the recent studies implicating activin-A in the modulation of experimental and human allergic asthma. Keywords: Activin-A, airway inflammation, airway tolerance, ALK4, allergic disorders, asthma, immune regulation, immunotherapies, regulatory T cells, TGF-β superfamily, Th2 cell responses.