Please use this identifier to cite or link to this item:
Title: Activin-A attenuates several human natural killer cell functions.
Austin 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, Victoria, Australia
Issue Date: 13-Jan-2009
Publication information: 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.
Gov't Doc #: 19141859
DOI: 10.1182/blood-2008-07-166926
Type: Journal Article
Subjects: Activins.metabolism.pharmacology.physiology
Cell Proliferation.drug effects
Cells, Cultured
Cytotoxicity, Immunologic.drug effects
Dendritic Cells.metabolism
Gene Expression Regulation
Immune Tolerance.drug effects
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

Files in This Item:
File Description SizeFormat 
19141859.pdf297.67 kBAdobe PDFThumbnail
Show full item record

Page view(s)

checked on Dec 9, 2022


checked on Dec 9, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.