Activin-A attenuates several human natural killer cell functions

Robson, N.C., Wei, H., McAlpine, T., Kirkpatrick, N., Cebon, J. and Maraskovsky, E. (2009) Activin-A attenuates several human natural killer cell functions. Blood, 113(14), pp. 3218-3225. (doi: 10.1182/blood-2008-07-166926)

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-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-γ) but not perforin or granzyme mRNA; (2) suppressing NK-cell IFN-γ 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robson, Dr Neil
• Authors: Robson, N.C., Wei, H., McAlpine, T., Kirkpatrick, N., Cebon, J., and Maraskovsky, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Blood
• Publisher: American Society of Hematology
• ISSN: 0006-4971
• ISSN (Online): 1528-0020