The inflammatory cytokine, GM-CSF, alters the developmental outcome of murine dendritic cells
AuthorZhan, Y; Vega-Ramos, J; Carrington, EM; Villadangos, JA; Lew, AM; Xu, Y
Source TitleEUROPEAN JOURNAL OF IMMUNOLOGY
University of Melbourne Author/sXU, YUEKANG; Carrington, Emma; Villadangos, Jose; Lew, Andrew; Zhan, Yifan; VEGA RAMOS, JAVIER
AffiliationThe Walter and Eliza Hall Institute of Medical Research
Department of Medical Biology
Department of Biochemistry and Molecular Biology
Document TypeJournal Article
CitationsZhan, Y., Vega-Ramos, J., Carrington, E. M., Villadangos, J. A., Lew, A. M. & Xu, Y. (2012). The inflammatory cytokine, GM-CSF, alters the developmental outcome of murine dendritic cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 42 (11), pp.2889-2900. https://doi.org/10.1002/eji.201242477.
Access StatusThis item is currently not available from this repository
NHMRC Grant codeNHMRC/1006428
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
The research outputs in this collection have been funded in whole or in part by the National Health and Medical Research Council (NHMRC).
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.
KeywordsGM-CSF; Flt3L; dendritic cells and differentiation
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