Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 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
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
blood-2007-03-080994v1
111/5/2733    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Robson, N. C.
Right arrow Articles by Maraskovsky, E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robson, N. C.
Right arrow Articles by Maraskovsky, E.
Related Collections
Right arrow Immunobiology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

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-{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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
Sponsor: Genentech BioOncology and and Biogen Idec
Blood Online is supported in part by
Genentech BioOncology and Biogen Idec
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020