Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Activin-A is a pleiotropic cytokine that participates in developmental, inflammatory, and tissue repair processes. Still, its effects on T helper (Th) cell-mediated immunity, critical for allergic and autoimmune diseases, are elusive. We provide evidence that endogenously produced activin-A suppresses antigen-specific Th2 responses and protects against airway hyperresponsiveness and allergic airway disease in mice. Importantly, we reveal that activin-A exerts suppressive function through induction of antigen-specific regulatory T cells that suppress Th2 responses in vitro and upon transfer in vivo. In fact, activin-A also suppresses Th1-driven responses, pointing to a broader immunoregulatory function. Blockade of interleukin 10 and transforming growth factor beta1 reverses activin-A-induced suppression. Remarkably, transfer of activin-A-induced antigen-specific regulatory T cells confers protection against allergic airway disease. This beneficial effect is associated with dramatically decreased maturation of draining lymph node dendritic cells. Therapeutic administration of recombinant activin-A during pulmonary allergen challenge suppresses Th2 responses and protects from allergic disease. Finally, we demonstrate that immune cells infiltrating the lungs from individuals with active allergic asthma, and thus nonregulated inflammatory response, exhibit significantly decreased expression of activin-A's responsive elements. Our results uncover activin-A as a novel suppressive factor for Th immunity and a critical controller of allergic airway disease.

Original publication

DOI

10.1084/jem.20082603

Type

Journal article

Journal

J Exp Med

Publication Date

03/08/2009

Volume

206

Pages

1769 - 1785

Keywords

Activins, Adult, Animals, Asthma, Encephalomyelitis, Autoimmune, Experimental, Humans, Immune Tolerance, In Vitro Techniques, Interleukin-10, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Transgenic, Middle Aged, Ovalbumin, Recombinant Proteins, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Th2 Cells, Transforming Growth Factor beta1, Young Adult