Activin-A: A New Piece in the Puzzle of Tolerance in Asthma
Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Aikaterini I Trochoutsou and Georgina Xanthou
Affiliation: Cellular Immunology Laboratory, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4, Soranou Efesiou street, Athens 115 27, Greece.
Keywords: Activin-A, airway inflammation, airway tolerance, ALK4, allergic disorders, asthma, immune regulation, immunotherapies,
regulatory T cells, TGF-β superfamily, Th2 cell responses.
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.
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