Open Access

ARTICLE

Production and function of activin A in human dendritic cells

Sara Scutera¹, Elena Riboldi², Roberta Daniele^1,2, Angela Rita Elia³, Tiziana Fraone³, Carlotta Castagnoli⁴, Mirella Giovarelli³, Tiziana Musso^1,*, Silvano Sozzani^2,*

1 Department of Public Health and Microbiology, University of Torino, Torino, Italy
2 Section of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy
3 Medicine and Experimental Oncology, University of Torino; Center for Experimental Research and Medical Studies (CERMS), S. Giovanni Battista Hospital, Torino, Italy
4 Department of Plastic Surgery and Burn Unit Skin Bank, CTO Hospital, Torino, Italy

* Corresponding Author: S. Sozani,

European Cytokine Network 2008, 19(1), 60-68. https://doi.org/10.1684/ecn.2008.0121

Accepted 11 February 2008;

Abstract

Activin A, a member of the transforming growth factor-b 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).

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Keywords

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