Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Robson, N.C. et al.

Neil C. Robson, David J. Phillips, Tristan McAlpine, Amanda Shin, Suzanne Svobodova, Tracey Toy, Vinochani Pillay, Naomi Kirkpatrick, Damien Zanker, Kathy Wilson, Imke Helling, Heng Wei, Weisan Chen, Jonathan Cebon, Eugene Maraskovsky,

Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production.

Activin-A is a transforming growth factor-beta (TGF-beta) superfamily member that plays a pivotal role in many developmental and reproductive processes. It is also involved in neuroprotection, apoptosis of tumor and some immune cells, wound healing, and cancer. Its role as an immune-regulating protein has not previously been described. Here we demonstrate for the first time that activin-A has potent autocrine effects on the capacity of human dendritic cells (DCs) to stimulate immune responses. Human monocyte-derived DCs (MoDCs) and the CD1c(+) and CD123(+) peripheral blood DC populations express both activin-A and the type I and II activin receptors. Furthermore, MoDCs and CD1c(+) myeloid DCs rapidly secrete high levels of activin-A after exposure to bacteria, specific toll-like receptor (TLR) ligands, or CD40 ligand (CD40L). Blocking autocrine activin-A signaling in DCs using its antagonist, follistatin, enhanced DC cytokine (IL-6, IL-10, IL-12p70, and tumor necrosis factor-alpha [TNF-alpha]) and chemokine (IL-8, IP-10, RANTES, and MCP-1) production during CD40L stimulation, but not TLR-4 ligation. Moreover, antagonizing DC-derived activin-A resulted in significantly enhanced expansion of viral antigen-specific effector CD8(+) T cells. These findings establish an immune-regulatory role for activin-A in DCs, highlighting the potential of antagonizing activin-A signaling in vivo to enhance vaccine immunogenicity.[1]

References

Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production. Robson, N.C., Phillips, D.J., McAlpine, T., Shin, A., Svobodova, S., Toy, T., Pillay, V., Kirkpatrick, N., Zanker, D., Wilson, K., Helling, I., Wei, H., Chen, W., Cebon, J., Maraskovsky, E. Blood (2008) [Pubmed]

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