Activin a as a mediator of nk-dendritic cell functional interactions

Pascal Seeger, Daniela Bosisio, Silvia Parolini, Raffaele Badolato, Angela Gismondi, Angela Santoni, Silvano Sozzani

Research output: Contribution to journalArticlepeer-review


The interaction of NK cells with dendritic cells (DCs) results in reciprocal cell activation through the interaction of membrane proteins and the release of soluble factors. In this article, we report that in NK-DC cocultures, among a set of 84 cytokines investigated, activin A was the second highest induced gene, with CXCL8 being the most upregulated one. Activin A is a member of the TGF-b superfamily and was previously shown to possess both proinflammatory and anti-inflammatory activities. In NK-DC cocultures, the induction of activin A required cell contact and was dependent on the presence of proinflammatory cytokines (i.e., IFN-g, TNF-A, and GM-CSF), as well as on NK cell-mediated DC killing. CD1+ DCs were the main activin A producer cells among myeloid blood DC subsets. In NK-DC cocultures, inhibition of activin A by follistatin, a natural inhibitory protein, or by a specific blocking Ab, resulted in the upregulation of proinflammatory cytokine release (i.e., IL-6, IL-8, TNF-A) by DCs and in the increase of DC maturation. In conclusion, our study reports that activin A, produced during NK-DC interactions, represents a relevant negative feedback mechanism that might function to prevent excessive immune activation by DCs.

Original languageEnglish
Pages (from-to)1241-1248
Number of pages8
JournalJournal of Immunology
Issue number3
Publication statusPublished - Feb 1 2014

ASJC Scopus subject areas

  • Immunology


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