title: Increased and long-term generation of dendritic cells with reduced function from IL-6-deficient bone marrow.
abstract: The importance of IL-6 in dendritic cell (DC) development and function has not been well defined. To establish the role of IL-6, we studied bone marrow-derived DC (BMDC) and freshly isolated splenic DC from IL-6(-/-)-transgenic mice. We found that although IL-6(-/-) bone marrow had a similar composition to that of wild-type (WT) mice, it generated up to 10 times more DC when cultured in GM-CSF. The difference persisted even when IL-6(-/-) and WT bone marrow were cultured together, excluding the possibility that the effects were simply due to different cytokine microenvironments. In comparison to WT BMDC, IL-6(-/-) BMDC captured at least as much Ag, had an equivalent surface phenotype, and matured similarly in response to LPS or CpG. However, IL-6(-/-) BMDC induced less T cell allostimulation and Ag-specific T cell activation, but only the former was related to their inability to generate IL-6. Although WT bone marrow cultures died within 4 wk, IL-6(-/-) cultures continued to generate BMDC for >120 days, although the BMDC became immature and less functional. In vivo, we found that IL-6(-/-) mice had similar numbers and types of splenic DC as WT mice, both normally and after treatment with either Flt-3 ligand or GM-CSF. These findings demonstrate that IL-6 has profound effects on DC development in vitro, although the number and subtype composition of DC are unaffected by the absence of IL-6 in vivo. Furthermore, secretion of IL-6 is critical to certain DC functions.
authors.affiliation: Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10024, USA.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Bleier
authors.forename: Venu G
authors.initials: VG
authors.lastname: Pillarisetty
authors.forename: Alaap B
authors.initials: AB
authors.lastname: Shah
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor