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

Robson, N.C. et al. (2008) Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production. Blood, 111(5), pp. 2733-2743. (doi: 10.1182/blood-2007-03-080994)

Abstract

Activin-A is a transforming growth factor-β (TGF-β) 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-α [TNF-α]) 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robson, Dr Neil
• Authors: 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., and Maraskovsky, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Blood
• Publisher: American Society of Hematology
• ISSN: 0006-4971
• ISSN (Online): 1528-0020