Immunostimulatory conventional dendritic cells evolve into regulatory macrophage-like cells
Immunostimulatory conventional dendritic cells evolve into regulatory macrophage-like cells
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DOI：
10.1182/blood-2011-11-392894
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发表时间：
2012-05-24
期刊：
影响因子：
20.3
通讯作者：
Cattral, Mark S.
中科院分区：
文献类型：
--
作者：
Diao, Jun;Mikhailova, Anastassia;Cattral, Mark S.
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. (Blood. 2012;119(21):4919-4927)
