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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2733-2743. Prepublished online as a Blood First Edition Paper on December 21, 2007; DOI 10.1182/blood-2007-03-080994. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-03-080994v1 111/5/2733    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robson, N. C. Articles by Maraskovsky, E. Search for Related Content PubMed PubMed Citation Articles by Robson, N. C. Articles by Maraskovsky, E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activin-A: a novel dendritic cell–derived cytokine that potently attenuates CD40 ligand–specific cytokine and chemokine production Neil C. Robson1, David J. Phillips2, Tristan McAlpine1, Amanda Shin1, Suzanne Svobodova1, Tracey Toy1, Vinochani Pillay1, Naomi Kirkpatrick1, Damien Zanker1, Kathy Wilson2, Imke Helling1, Heng Wei1, Weisan Chen1, Jonathan Cebon1, and Eugene Maraskovsky3 1 Ludwig Institute for Cancer Research, Austin Health, Heidelberg; 2 Monash Institute of Medical Research, Monash University, Clayton; and 3 CSL Limited, Parkville, Australia 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- [TNF-]) 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Xia and A. L Schneyer The biology of activin: recent advances in structure, regulation and function J. Endocrinol., July 1, 2009; 202(1): 1 - 12. [Abstract] [Full Text] [PDF] L. Salogni, T. Musso, D. Bosisio, M. Mirolo, V. R. Jala, B. Haribabu, M. Locati, and S. Sozzani Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14 Blood, June 4, 2009; 113(23): 5848 - 5856. [Abstract] [Full Text] [PDF] N. C. Robson, H. Wei, T. McAlpine, N. Kirkpatrick, J. Cebon, and E. Maraskovsky Activin-A attenuates several human natural killer cell functions Blood, April 2, 2009; 113(14): 3218 - 3225. [Abstract] [Full Text] [PDF]

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