IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFN?.
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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 (M?) or dendritic cells (DC). A wide spectrum of M? 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(-) M? (IL-34-M?). Upon LPS stimulation, IL-34-M? exhibit an IL-10(high) IL-12(low) M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-M? 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-M? are phenotypically and functionally similar to M-CSF-M?. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive M?. Moreover, the generation of IL-34-M? 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 IFN? and GM-CSF prevent the generation of immunosuppressive M? induced by IL-34. IFN? also switches established IL-34-M? into immunostimulatory M?. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFN? and GM-CSF prevent this effect.
SUBMITTER: Foucher ED
PROVIDER: S-EPMC3568045 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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