GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c+MHCII+ Macrophages and Dendritic Cells

Abstract

Dendritic cells (DCs) are key players in the immune system. Much of their biology has been elucidated via culture systems in which hematopoietic precursors differentiate into DCs under the aegis of cytokines. A widely used protocol involves the culture of murine bone marrow (BM) cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) to generate BM-derived DCs (BMDCs). BMDCs express CD11c and MHC class II (MHCII) molecules and share with DCs isolated from tissues the ability to present exogenous antigens to T cells and to respond to microbial stimuli by undergoing maturation. We demonstrate that CD11c(+)MHCII(+) BMDCs are in fact a heterogeneous group of cells that comprises conventional DCs and monocyte-derived macrophages. DCs and macrophages in GM-CSF cultures both undergo maturation upon stimulation with lipopolysaccharide but respond differentially to the stimulus and remain separable entities. These results have important implications for the interpretation of a vast array of data obtained with DC culture systems.

Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

“…The GM-CSF-expanded DCs were 85-90% CD11C + , and 45% were CD11c + MHC class II high . This finding is consistent with the recent demonstration that GM-CSF-expanded BMDCs are a heterogeneous population of DCs and monocytederived macrophages (21). Indeed, we found that FHES also enhanced TGF-b production by FLT3L-expanded BMDCs and M-CSF-expanded macrophages (data not shown), suggesting that FHES induces anti-inflammatory cytokine production by macrophages and DCs.…”

Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity

“…As illustrated in Figure 1C neg cells (Supplemental Figure 1B), which resemble the macrophage/monocyte population described by Helft et al (30). Injection of blood MoDC or TADC loaded with alloIgG-IC into the tumor-resected mice from which they were derived failed to protect against tumor recurrence ( Figure 1D).…”

CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells

“…Unexpectedly, we showed that CD9 deficiency did not affect Ag presentation by Flt3L-dependent conventional BMDCs. Recently, it has been suggested that BMDC cultures generated with GM-CSF are heterogeneous, containing CD11c ϩ MHC-II ϩ conventional DCs and monocyte-derived macrophages (63). GM-CSF-dependent BMDCs resemble monocyte-derived DCs (MoDCs), which constitute specialized inflammatory DCs, although monocytes can also be precursors of different DC subsets under steady-state conditions (53,54).…”