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IL-34 and CSF-1 display an equivalent macrophage differentiation ability but a different polarization potential

2018; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-18433-4

2045-2322

Sonia Boulakirba, Anja Pfeifer, Rana Mhaidly, Sandrine Obba, Michael Goulard, Thomas M. Schmitt, Paul Chaintreuil, Anne Calleja, Nathan Furstoss, François Orange, Sandra Lacas‐Gervais, Laurent Boyer, Sandrine Marchetti, Els Verhoeyen, Fréderic Luciano, Guillaume Robert, Patrick Auberger, Arnaud Jacquel,

Immune Response and Inflammation

Abstract CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in the signaling pathways triggered by both ligands in human monocytes. IL-34 promotes the differentiation and survival of monocytes, macrophages and osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that differences exist in the effect of both cytokines. In the present study, we compared the differentiation and polarization abilities of human primary monocytes in response to CSF-1 or IL-34. CSF-1R engagement by one or the other ligands leads to AKT and caspase activation and autophagy induction through expression and activation of AMPK and ULK1. As no differences were detected on monocyte differentiation, we investigated the effect of CSF-1 and IL-34 on macrophage polarization into the M1 or M2 phenotype. We highlighted a striking increase in IL-10 and CCL17 secretion in M1 and M2 macrophages derived from IL-34 stimulated monocytes, respectively, compared to CSF-1 stimulated monocytes. Variations in the secretome induced by CSF-1 or IL-34 may account for their different ability to polarize naïve T cells into Th1 cells. In conclusion, our findings indicate that CSF-1 and IL-34 exhibit the same ability to induce human monocyte differentiation but may have a different ability to polarize macrophages.