Production and function of activin A in human dendritic cells

Sara Scutera, Elena Riboldi, Roberta Daniele, Angela Rita Elia, Tiziana Fraone, Carlotta Castagnoli, Mirella Giovarelli, Tiziana Musso, Silvano Sozzani

Research output: Contribution to journalArticlepeer-review

Abstract

Activin A, a member of the transforming growth factor-β 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 dexametha sone 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).

Original languageEnglish
Pages (from-to)60-68
Number of pages9
JournalEuropean Cytokine Network
Volume19
Issue number1
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Activin A
  • Dendritic cells
  • Follistatin
  • Langerhans cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Biochemistry

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