title: IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ.
abstract: IL-34 is a recently identified cytokine that signals via the M-CSF receptor and promotes monocyte survival. Depending on the environment, monocytes can differentiate into macrophages (Mφ) or dendritic cells (DC). A wide spectrum of Mφ and DC subsets, with distinct phenotypes and functions, has been described. To date, the phenotype of monocytes exposed to IL-34 remains unexplored. We report here that IL-34 induces the differentiation of monocytes into CD14(high) CD163(high) CD1a(-) Mφ (IL-34-Mφ). Upon LPS stimulation, IL-34-Mφ exhibit an IL-10(high) IL-12(low) M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-Mφ exhibit poor T cell costimulatory properties, and have potent immunosuppressive properties (decrease of TCR-stimulated T cell proliferation). For all the parameters analyzed, IL-34-Mφ are phenotypically and functionally similar to M-CSF-Mφ. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive Mφ. Moreover, the generation of IL-34-Mφ is mediated through the M-CSF receptor, is independent of endogenous M-CSF consumption and is potentiated by IL-6. In an attempt to identify strategies to prevent a deleterious M2 cell accumulation in some pathological situations, we observed that IFNγ and GM-CSF prevent the generation of immunosuppressive Mφ induced by IL-34. IFNγ also switches established IL-34-Mφ into immunostimulatory Mφ. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFNγ and GM-CSF prevent this effect.
authors: LUNAM Université, Université d'Angers, Angers, France.
authors: Etienne D
authors: ED
authors: Foucher
authors: Simon
authors: S
authors: Blanchard
authors: Laurence
authors: L
authors: Preisser
authors: Erwan
authors: E
authors: Garo
authors: Norbert
authors: N
authors: Ifrah
authors: Philippe
authors: P
authors: Guardiola
authors: Yves
authors: Y
authors: Delneste
authors: Pascale
authors: P
authors: Jeannin
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D018925:Chemokines / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics
chemical_list: D018925:Chemokines; C529076:IL34 protein, human; D007378:Interleukins; D019707:Receptors, Chemokine; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor