Production and function of activin A in human dendritic cells.
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).
Scutera
Sara
S
Department of Public Health and Microbiology, University of Torino, Torino, Italy.
Riboldi
Elena
E
Daniele
Roberta
R
Elia
Angela Rita
AR
Fraone
Tiziana
T
Castagnoli
Carlotta
C
Giovarelli
Mirella
M
Musso
Tiziana
T
Sozzani
Silvano
S
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
D016207:Cytokines; D038681:Follistatin; D015850:Interleukin-6; D008070:Lipopolysaccharides; C422405:activin A; D028341:Activins