The inflammatory cytokine, GM-CSF, alters the developmental outcome of murine dendritic cells
- Author(s)
- Zhan, YF; Vega-Ramos, J; Carrington, EM; Villadangos, JA; Lew, AM; Xu, YK;
- Details
- Publication Year 2012-11,Volume 42,Issue #11,Page 2889-2900
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Fms-like tyrosine kinase 3 ligand (Flt3L) is a major cytokine that drives development of dendritic cells (DCs) under steady state, whereas GM-CSF becomes a prominent influence on differentiation during inflammation. The influence GM-CSF exerts on Flt3L-induced DC development has not been thoroughly examined. Here, we report that GM-CSF alters Flt3L-induced DC development. When BM cells were cultured with both Flt3L and GM-CSF, few CD8+ equivalent DCs or plasmacytoid DCs developed compared to cultures supplemented with Flt3L alone. The disappearance of these two cell subsets in GM-CSF + Flt3L culture was not a result of simple inhibition of their development, but a diversion of the original differentiation trajectory to form a new cell population. As a consequence, both DC progeny and their functions were altered. The effect of GM-CSF on DC subset development was confirmed in vivo. First, the CD8+ DC numbers were increased under GM-CSF deficiency (when either GM-CSF or its receptor was ablated). Second, this population was decreased under GM-CSF hyperexpression (by transgenesis or by Listeria infection). Our finding that GM-CSF dominantly changes the regulation of DC development in vitro and in vivo has important implications for inflammatory diseases or GM-CSF therapy.
- Publisher
- WILEY-BLACKWELL
- Keywords
- Dendritic cells and differentiation;Flt3L;GM-CSF
- Research Division(s)
- Immunology
- Publisher's Version
- https://doi.org/10.1002/eji.201242477
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Creation Date: 2012-11-01 12:00:00