title: Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14.
abstract: Activin A is a dimeric protein, member of the transforming growth factor (TGF)-beta family that plays a crucial role in wound repair and in fetal tolerance. Emerging evidence also proposes activin A as a key mediator in inflammation. This study reports that activin A induces the directional migration of immature myeloid dendritic cells (iDCs) through the activation of ALK4 and ActRIIA receptor chains. Conversely, activin A was not active on plasmacytoid dendritic cells (DCs) or mature myeloid DCs. iDC migration to activin A was phosphatidylinositol 3-kinase gamma-dependent, Bordetella pertussis toxin- and cycloheximide-sensitive, and was inhibited by M3, a viral-encoded chemokine-binding protein. In a real-time video microscopy-based migration assay, activin A induced polarization of iDCs, but not migration. These characteristics clearly differentiated the chemotactic activities of activin A from TGF-beta and classic chemokines. By the use of combined pharmacologic and low-density microarray analysis, it was possible to define that activin-A-induced migration depends on the selective and polarized release of 2 chemokines, namely CXC chemokine ligands 12 and 14. This study extends the proinflammatory role of activin A to DC recruitment and provides a cautionary message about the reliability of the in vitro chemotaxis assays in discriminating direct versus indirect chemotactic agonists.
authors.affiliation: Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Salogni
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.forename: Daniela
authors.initials: D
authors.lastname: Bosisio
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirolo
authors.forename: Venkatakrishna R
authors.initials: VR
authors.lastname: Jala
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani