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In this article, we report that in NK\u2013DC 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-\u03b2 superfamily and was previously shown to possess both proinflammatory and anti-inflammatory activities. In NK\u2013DC cocultures, the induction of activin A required cell contact and was dependent on the presence of proinflammatory cytokines (i.e., IFN-\u03b3, TNF-\u03b1, and GM-CSF), as well as on NK cell\u2013mediated DC killing. CD1+ DCs were the main activin A producer cells among myeloid blood DC subsets. In NK\u2013DC 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-\u03b1) by DCs and in the increase of DC maturation. In conclusion, our study reports that activin A, produced during NK\u2013DC interactions, represents a relevant negative feedback mechanism that might function to prevent excessive immune activation by DCs.<\/jats:p>","DOI":"10.4049\/jimmunol.1301487","type":"journal-article","created":{"date-parts":[[2014,1,7]],"date-time":"2014-01-07T04:18:05Z","timestamp":1389068285000},"page":"1241-1248","source":"Crossref","is-referenced-by-count":29,"title":["Activin A as a Mediator of NK\u2013Dendritic Cell Functional Interactions"],"prefix":"10.1093","volume":"192","author":[{"given":"Pascal","family":"Seeger","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , 25123 Brescia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Bosisio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , 25123 Brescia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Parolini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , 25123 Brescia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Badolato","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine \u201cAngelo Nocivelli,\u201d University of Brescia , 25123 Brescia,","place":["Italy"]},{"name":"Department of Clinical and Experimental Sciences, University of Brescia , 25123 Brescia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Gismondi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, La Sapienza University , 00161 Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Santoni","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, La Sapienza University , 00161 Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Sozzani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , 25123 Brescia,","place":["Italy"]},{"name":"Humanitas Clinical and Research Center , 20089 Rozzano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,1]]},"reference":[{"key":"2025032404095372000_r1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/7403","article-title":"Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo","volume":"5","author":"Fernandez","year":"1999","journal-title":"Nat. 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