title: Activin A as a mediator of NK-dendritic cell functional interactions.
abstract: 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-β 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-γ, TNF-α, 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-α) 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.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy;
authors.forename: Pascal
authors.initials: P
authors.lastname: Seeger
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
authors.forename: Angela
authors.initials: A
authors.lastname: Gismondi
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
mesh_terms: D028341:Activins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004285:Dogs; D025461:Feedback, Physiological; D038681:Follistatin / Q000494:pharmacology; D022861:Hermanski-Pudlak Syndrome / Q000473:pathology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D019409:Interleukin-15 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D055607:Receptors, Natural Killer Cell / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D000097802:CD83 Antigen
chemical_list: D028341:Activins; D015703:Antigens, CD; D051940:B7-2 Antigen; D016207:Cytokines; D038681:Follistatin; D007136:Immunoglobulins; D019409:Interleukin-15; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D055607:Receptors, Natural Killer Cell; D000097802:CD83 Antigen; C497964:CD86 protein, human; C508606:CXCL8 protein, human; C422405:activin A