First Author | Bleier JI | Year | 2004 |
Journal | J Immunol | Volume | 172 |
Issue | 12 | Pages | 7408-16 |
PubMed ID | 15187118 | Mgi Jnum | J:90835 |
Mgi Id | MGI:3044851 | Doi | 10.4049/jimmunol.172.12.7408 |
Citation | Bleier JI, et al. (2004) Increased and long-term generation of dendritic cells with reduced function from IL-6-deficient bone marrow. J Immunol 172(12):7408-16 |
abstractText | 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. |