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 language | English |
|---|---|
| Pages (from-to) | 5848-5856 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 113 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 2009 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. / Salogni, Laura; Musso, Tiziana; Bosisio, Daniela; Mirolo, Massimiliano; Jala, Venkatakrishna R.; Haribabu, Bodduluri; Locati, Massimo; Sozzani, Silvano.
In: Blood, Vol. 113, No. 23, 2009, p. 5848-5856.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14
AU - Salogni, Laura
AU - Musso, Tiziana
AU - Bosisio, Daniela
AU - Mirolo, Massimiliano
AU - Jala, Venkatakrishna R.
AU - Haribabu, Bodduluri
AU - Locati, Massimo
AU - Sozzani, Silvano
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2008-12-194597
DO - 10.1182/blood-2008-12-194597
M3 - Article
C2 - 19339694
AN - SCOPUS:67651097892
VL - 113
SP - 5848
EP - 5856
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -