| First Author | Diao J | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 21 | Pages | 4919-27 |
| PubMed ID | 22490680 | Mgi Jnum | J:185155 |
| Mgi Id | MGI:5427540 | Doi | 10.1182/blood-2011-11-392894 |
| Citation | Diao J, et al. (2012) Immunostimulatory conventional dendritic cells evolve into regulatory macrophage-like cells. Blood 119(21):4919-27 |
| abstractText | 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. |
