Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14

Activin A is a dimeric protein, member of
the transforming growth factor (TGF)–
family that plays a crucial role in wound
repair and in fetal tolerance. Emerging
evidence also proposes activin Aas 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
–dependent, Bordetella pertussis toxin–
and cycloheximide-sensitive, and was
inhibited by M3, a viral-encoded chemokinebinding
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- 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.