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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 (MQ) or dendritic cells (DC). A wide spectrum of MQ 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 2 MQ (IL-34-MQ). Upon LPS stimulation, IL-34-MQ exhibit an IL-10 high IL-12 low M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-MQ 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-MQ are phenotypically and functionally similar to M-CSF-MQ. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive MQ. Moreover, the generation of IL-34-MQ 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 IFNc and GM-CSF prevent the generation of immunosuppressive MQ induced by IL-34. IFNc also switches established IL-34-MQ into immunostimulatory MQ. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFNc and GM-CSF prevent this effect.
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https://www.hal.inserm.fr/inserm-03377784
Contributor : Simon Blanchard Connect in order to contact the contributor
Submitted on : Thursday, October 14, 2021 - 12:11:43 PM
Last modification on : Wednesday, November 10, 2021 - 3:32:04 PM

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Etienne Foucher, Simon Blanchard, Laurence Preisser, Erwan Garo, Norbert Ifrah, et al.. IL-34 Induces the Differentiation of Human Monocytes into Immunosuppressive Macrophages. Antagonistic Effects of GM-CSF and IFNγ. PLoS ONE, Public Library of Science, 2013, 8 (2), pp.e56045. ⟨10.1371/journal.pone.0056045⟩. ⟨inserm-03377784⟩

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