Transcription profiling of mouse dendritic cell differentiation from dendritic cell progenitor in vitro
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Thomas Hieronymus
PROVIDER: E-GEOD-575 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Progressive and controlled development of mouse dendritic cells from Flt3+CD11b+ progenitors in vitro.
Hieronymus Thomas T Gust Tatjana C TC Kirsch Ralf D RD Jorgas Thorsten T Blendinger Gitta G Goncharenko Mykola M Supplitt Kamilla K Rose-John Stefan S Müller Albrecht M AM Zenke Martin M
Journal of immunology (Baltimore, Md. : 1950) 20050301 5
Dendritic cells (DC) represent key regulators of the immune system, yet their development from hemopoietic precursors is poorly defined. In this study, we describe an in vitro system for amplification of a Flt3(+)CD11b(+) progenitor from mouse bone marrow with specific cytokines. Such progenitor cells develop into both CD11b(+) and CD11b(-) DC, and CD8alpha(+) and CD8alpha(-) DC in vivo. Furthermore, with GM-CSF, these progenitors synchronously differentiated into fully functional DC in vitro. T ...[more]
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Project description:FLT3+CD11b+ DC progenitor was amplified in vitro from mouse bone marrow. DC were differentiated using GM-CSF and analyzed at day 7 and day 10 of differentiation and after 16h TNFalpha stimulation at day 10 Keywords: time-course
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Project description:Dendritic cells (DC) develop from hematopoietic stem cells, which is guided by instructive signals through cytokines. DC development progresses from multipotent progenitors (MPP) via common DC progenitors (CDP) into DC. Flt3 ligand (Flt3L) signaling via the Flt3/Stat3 pathway is of pivotal importance for DC development under steady state conditions. Additional factors produced during steady state or inflammation, such as TGF-beta1 or GM-CSF, also influence the differentiation potential of MPP and CDP. Here, we studied how gp130, GM-CSF and TGF-beta1 signaling influence DC lineage commitment from MPP to CDP and further into DC. We observed that activation of gp130 signaling promotes expansion of MPP. Additionally, gp130 signaling inhibited Flt3L-driven DC differentiation, but had little effect on GM-CSF-driven DC development. The inflammatory cytokine GM-CSF induces differentiation of MPP into inflammatory DC and blocks steady state DC development. Global transcriptome analysis revealed a GM-CSF-driven gene expression repertoire that primes MPP for differentiation into inflammatory DC. Finally, TGF-beta1 induces expression of DC-lineage affiliated genes in MPP, including Flt3, Irf-4 and Irf-8. Under inflammatory conditions, however, the effect of TGF- beta1 is altered: Flt3 is not upregulated, indicating that an inflammatory environment inhibits steady state DC development. Altogether, our data indicate that distinct cytokine signals produced during steady state or inflammation have a different outcome on DC lineage commitment and differentiation.
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Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1) Three two-condition experiments, control (N) vs tolerogenic DC with three different treatments. Pool of 4 indivuduals for each condition. One replicate per array.
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