Immunostimulatory conventional dendritic cells evolve into regulatory macrophage-like cells.
Blood
; 119(21): 4919-27, 2012 May 24.
Article
de En
| MEDLINE
| ID: mdl-22490680
ABSTRACT
Dendritic cell (DC) homeostasis in peripheral tissues reflect a balance between DC generation, migration, and death. The current model of DC ontogeny indicates that pre-cDCs are committed to become terminal conventional DCs (cDCs). Here, we report the unexpected finding that proliferating immunostimulatory CD11c(+) MHC class II(+) cDCs derived from pre-cDCs can lose their DC identity and generate progeny that exhibit morphologic, phenotypic, and functional characteristics of regulatory macrophages. DC-derived-macrophages (DC-d-Ms) potently suppress T-cell responses through the production of immunosuppressive molecules including nitric oxide, arginase, and IL-10. Relative deficiency of granulocyte-macrophage colony stimulating factor (GM-CSF) provided a permissive signal for DC-d-M generation. Using a transgenic mouse model that allows tracking of CD11c(+) cells in vivo, we found that DC-d-M development occurs commonly in cancer, but not in lymphoid or nonlymphoid tissues under steady-state conditions. We propose that this developmental pathway serves as an alternative mechanism of regulating DC homeostasis during inflammatory processes.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules dendritiques
/
Différenciation cellulaire
/
Macrophages
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Blood
Année:
2012
Type de document:
Article
Pays d'affiliation:
Canada