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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3218-3225. Prepublished online as a Blood First Edition Paper on January 13, 2009; DOI 10.1182/blood-2008-07-166926. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-166926v1 113/14/3218    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 attenuates several human natural killer cell functions Neil C. Robson1, Heng Wei1, Tristan McAlpine1, Naomi Kirkpatrick1, Jonathan Cebon1,*, and Eugene Maraskovsky2,* 1 Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg; and 2 CSL Limited, Bio21 Institute, Parkville, Australia 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-β), but DCs do not appear to produce TGF-β. We have previously shown that activated human DCs produce large amounts of activin-A, a TGF-β superfamily member, which autoregulates DC function. The present report shows that NKcells 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-) but not perforin or granzyme mRNA; (2) suppressing NK-cell IFN- production as potently as TGF-β; and (3) suppressing NK-cell CD25 expression and proliferation and sculpting NK-cell cytokine and chemokine profiles. Interestingly, unlike TGF-β, 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Semitekolou, T. Alissafi, M. Aggelakopoulou, E. Kourepini, H. H. Kariyawasam, A. B. Kay, D. S. Robinson, C. M. Lloyd, V. Panoutsakopoulou, and G. Xanthou Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease J. Exp. Med., August 3, 2009; 206(8): 1769 - 1785. [Abstract] [Full Text] [PDF]

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