The inflammatory cytokine, GM‐CSF, alters the developmental outcome of murine dendritic cells

• Published in: European journal of immunology 2012-11, Vol.42 (11), p.2889-2900
• Main Authors: Zhan, Yifan, Vega‐Ramos, Javier, Carrington, Emma M., Villadangos, Jose A., Lew, Andrew M., Xu, Yuekang
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Cell Differentiation - immunology; Cytokines; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic cells and differentiation; Flow Cytometry; Flt3L; fms-Like Tyrosine Kinase 3 - immunology; GM‐CSF; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Inflammation - immunology; Inflammation - pathology; Interleukin-10 - immunology; Interleukin-12 - immunology; Membrane Proteins - immunology; Membrane Proteins - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reactive Oxygen Species - immunology; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242477

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.