The inflammatory cytokine, GM-CSF, alters the developmental outcome of murine dendritic cells.
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.
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. zhan@wehi.edu.au
Yifan
Y
Zhan
Javier
J
Vega-Ramos
Emma M
EM
Carrington
Jose A
JA
Villadangos
Andrew M
AM
Lew
Yuekang
Y
Xu
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016753:Interleukin-10; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051941:fms-Like Tyrosine Kinase 3