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

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 suppress...

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Autores principales: Semitekolou, Maria, Alissafi, Themis, Aggelakopoulou, Maria, Kourepini, Evangelia, Kariyawasam, Harsha H., Kay, Antony B., Robinson, Douglas S., Lloyd, Clare M., Panoutsakopoulou, Vily, Xanthou, Georgina
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722168/
https://www.ncbi.nlm.nih.gov/pubmed/19620629
http://dx.doi.org/10.1084/jem.20082603
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author Semitekolou, Maria
Alissafi, Themis
Aggelakopoulou, Maria
Kourepini, Evangelia
Kariyawasam, Harsha H.
Kay, Antony B.
Robinson, Douglas S.
Lloyd, Clare M.
Panoutsakopoulou, Vily
Xanthou, Georgina
author_facet Semitekolou, Maria
Alissafi, Themis
Aggelakopoulou, Maria
Kourepini, Evangelia
Kariyawasam, Harsha H.
Kay, Antony B.
Robinson, Douglas S.
Lloyd, Clare M.
Panoutsakopoulou, Vily
Xanthou, Georgina
author_sort Semitekolou, Maria
collection PubMed
description 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 β1 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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spelling pubmed-27221682010-02-03 Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease Semitekolou, Maria Alissafi, Themis Aggelakopoulou, Maria Kourepini, Evangelia Kariyawasam, Harsha H. Kay, Antony B. Robinson, Douglas S. Lloyd, Clare M. Panoutsakopoulou, Vily Xanthou, Georgina J Exp Med Article 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 β1 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. The Rockefeller University Press 2009-08-03 /pmc/articles/PMC2722168/ /pubmed/19620629 http://dx.doi.org/10.1084/jem.20082603 Text en © 2009 Semitekolou et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Semitekolou, Maria
Alissafi, Themis
Aggelakopoulou, Maria
Kourepini, Evangelia
Kariyawasam, Harsha H.
Kay, Antony B.
Robinson, Douglas S.
Lloyd, Clare M.
Panoutsakopoulou, Vily
Xanthou, Georgina
Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title_full Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title_fullStr Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title_full_unstemmed Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title_short Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
title_sort activin-a induces regulatory t cells that suppress t helper cell immune responses and protect from allergic airway disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722168/
https://www.ncbi.nlm.nih.gov/pubmed/19620629
http://dx.doi.org/10.1084/jem.20082603
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