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Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease.

Authors: Semitekolou, M  Alissafi, T  Aggelakopoulou, M  Kourepini, E  Kariyawasam, HH  Kay, AB  Robinson, DS  Lloyd, CM  Panoutsakopoulou, V  Xanthou, G 
Citation: Semitekolou M, etal., J Exp Med. 2009 Aug 3;206(8):1769-85. Epub 2009 Jul 20.
Pubmed: (View Article at PubMed) PMID:19620629
DOI: Full-text: DOI:10.1084/jem.20082603

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.

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CRRD Object Information
CRRD ID: 4145132
Created: 2010-10-26
Species: All species
Last Modified: 2010-10-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.