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

Laura Salogni, Tiziana Musso, Daniela Bosisio, Massimiliano Mirolo, Venkatakrishna R. Jala, Bodduluri Haribabu, Massimo Locati, Silvano Sozzani

Research output: Contribution to journalArticlepeer-review

Abstract

Activin A is a dimeric protein, member of the transforming growth factor (TGF)-β 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 γ-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-β 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.

Original languageEnglish
Pages (from-to)5848-5856
Number of pages9
JournalBlood
Volume113
Issue number23
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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