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

作者：Salogni Laura; Musso Tiziana; Bosisio Daniela; Mirolo Massimiliano; Jala Venkatakrishna R; Haribabu Bodduluri; Locati Massimo; Sozzani Silvano^*

来源：Blood, 2009, 113(23): 5848-5856.

DOI：10.1182/blood-2008-12-194597

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. (Blood. 2009; 113: 5848-5856)

• 出版日期2009-6-4