title: Immunostimulatory conventional dendritic cells evolve into regulatory macrophage-like cells.
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.
authors.affiliation: Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Diao
authors.forename: Anastassia
authors.initials: A
authors.lastname: Mikhailova
authors.forename: Michael
authors.initials: M
authors.lastname: Tang
authors.forename: Hongtao
authors.initials: H
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cattral
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018845:CD11 Antigens / Q000235:genetics / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D018845:CD11 Antigens