title: Production and function of activin A in human dendritic cells.
abstract: Activin A, a member of the transforming growth factor-beta superfamily, has a role in tissue repair and inflammation. In our previous studies, we identified by immunohistochemistry DC-SIGN(+) dendritic cells as a source of activin A in vivo. The present study was aimed at investigating activin A production by dendritic cells (DC) in vitro and its function. Here we demonstrate that monocyte-derived DC (Mo-DC) released abundant levels of activin A during the maturation process induced by TLR agonists, bacteria (B. henselae, S. thyphimurium), TNF and CD40L. Activin A was also induced in monocyte-derived Langerhans cells (LC) and in blood myeloid DC by LPS and/or CD40L stimulation, but not in blood plasmacytoid DC following stimulation with influenza virus. Activin A production by DC was selectively down-regulated by anti-inflammatory molecules such as dexamethasone or IL-10. Neutralization of endogenous activin A using its inhibitor follistatin, or the addition of exogenous activin A during LPS maturation did not affect Mo-DC maturation marker expression, cytokine release or allostimulatory function. However, Mo-DC matured with LPS in the presence of exogenous activin A displayed a higher FITC-dextran uptake, similar to that of immature DC. Moreover, activin A promoted monocyte differentiation to DC and reversed the inhibitory effects of IL-6 on DC differentiation of monocytes. These findings demonstrate that different subsets of DC release activin A, a cytokine that promotes DC generation, and affects the ability of mature DC to take up antigens (Ags).
authors.affiliation: Department of Public Health and Microbiology, University of Torino, Torino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Scutera
authors.forename: Elena
authors.initials: E
authors.lastname: Riboldi
authors.forename: Roberta
authors.initials: R
authors.lastname: Daniele
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Elia
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fraone
authors.forename: Carlotta
authors.initials: C
authors.lastname: Castagnoli
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
mesh_terms: D028341:Activins / Q000737:chemistry / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D038681:Follistatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology; D008070:Lipopolysaccharides / Q000737:chemistry; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D038681:Follistatin; D015850:Interleukin-6; D008070:Lipopolysaccharides; C422405:activin A; D028341:Activins