Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10748
Title: Activin-A attenuates several human natural killer cell functions.
Authors: Robson, Neil C;Wei, Heng;McAlpine, Tristan;Kirkpatrick, Naomi;Cebon, Jonathan S;Maraskovsky, Eugene
Affiliation: Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Australia. neil.robson@ludwig.edu.au
Issue Date: 13-Jan-2009
Citation: Blood 2009; 113(14): 3218-25
Abstract: Dendritic-cell (DC) and natural killer (NK)-cell interactions are critical in sculpting the adaptive immune response. However, the mechanisms by which DCs down-regulate NK-cell functions are not well understood. NK-cell function is inhibited by transforming growth factor beta (TGF-beta), but DCs do not appear to produce TGF-beta. We have previously shown that activated human DCs produce large amounts of activin-A, a TGF-beta superfamily member, which autoregulates DC function. The present report shows that NK-cells express type I and II activin receptors and that activin-A triggers NK-cell Smad 2/3 signaling. Furthermore, activin-A directly regulates NK cell functions by (1) down-regulating the T-box transcription factor T-bet and interferon gamma (IFN-gamma) but not perforin or granzyme mRNA; (2) suppressing NK-cell IFN-gamma production as potently as TGF-beta; and (3) suppressing NK-cell CD25 expression and proliferation and sculpting NK-cell cytokine and chemokine profiles. Interestingly, unlike TGF-beta, activin-A weakly down-regulates the NK-cell natural cytotoxicity receptors (NCRs) NKp30 and NKG2D but does not attenuate their cytotoxic function. These findings provide the first evidence for a novel immune regulatory role of activin-A during DC-mediated NK-cell regulation, highlighting the potential of antagonizing activin-A signaling in vivo to enhance NK cell-mediated immune functions and adaptive immunity.
Internal ID Number: 19141859
URI: http://ahro.austin.org.au/austinjspui/handle/1/10748
DOI: 10.1182/blood-2008-07-166926
URL: http://www.ncbi.nlm.nih.gov/pubmed/19141859
Type: Journal Article
Subjects: Activins.metabolism.pharmacology.physiology
Cell Proliferation.drug effects
Cells, Cultured
Cytotoxicity, Immunologic.drug effects
Dendritic Cells.metabolism
Gene Expression Regulation
Humans
Immune Tolerance.drug effects
Interferon-gamma.metabolism
Jurkat Cells
K562 Cells
Killer Cells, Natural.drug effects.immunology.metabolism.physiology
Receptors, Transforming Growth Factor beta.genetics
Signal Transduction.genetics
Smad Proteins.metabolism.physiology
Appears in Collections:Journal articles

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