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

2009 ◽  
Vol 206 (8) ◽  
pp. 1769-1785 ◽  
Author(s):  
Maria Semitekolou ◽  
Themis Alissafi ◽  
Maria Aggelakopoulou ◽  
Evangelia Kourepini ◽  
Harsha H. Kariyawasam ◽  
...  

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.

Immunity ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 660-674 ◽  
Author(s):  
Joanne E. Konkel ◽  
Dunfang Zhang ◽  
Peter Zanvit ◽  
Cheryl Chia ◽  
Tamsin Zangarle-Murray ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiangping Song ◽  
Jie Huang ◽  
Xiao Chen ◽  
Xiao Teng ◽  
Zhizhao Song ◽  
...  

Abstract To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4+ T cells to express Fork head protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4+ T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation.


2008 ◽  
Vol 181 (10) ◽  
pp. 6942-6954 ◽  
Author(s):  
Mark S. Wilson ◽  
John T. Pesce ◽  
Thirumalai R. Ramalingam ◽  
Robert W. Thompson ◽  
Allen Cheever ◽  
...  

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