Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production
| Autor: | Neil C Robson, Tracey Toy, Heng Wei, Tristan McAlpine, Kathy Wilson, David James Phillips, Weisan Chen, Damien Zanker, Naomi Kirkpatrick, Eugene Maraskovsky, Amanda Shin, Imke Helling, Vinochani Pillay, Suzanne Svobodova, Jonathan Cebon |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Chemokine Follistatin medicine.medical_treatment Bone Morphogenetic Protein 7 Immunology CD40 Ligand chemical and pharmacologic phenomena Receptors Cell Surface Bone Morphogenetic Protein 4 Cell Separation Biology CD8-Positive T-Lymphocytes Biochemistry Epitopes Immune system Transforming Growth Factor beta medicine Humans Autocrine signalling Cell Proliferation Cell Biology Hematology Activin receptor Dendritic cell Dendritic Cells Myostatin Cell biology Activins Cytokine Gene Expression Regulation embryonic structures Bone Morphogenetic Proteins biology.protein Tumor necrosis factor alpha Chemokines hormones hormone substitutes and hormone antagonists |
| Zdroj: | Blood. 111(5) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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