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

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.

Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration

“…CSF-1 and IL-34 both bind to CSF1R and are both expressed in the brain, but the cell signaling events differ between the two ligands. 44,45 We observed increased CSF-1 mRNA levels in the brains of PD patients compared to age-matched controls ( Figure 1B), whereas we found no difference in IL-34 mRNA levels ( Figure 1C). Further, CSF-1 gene expression and protein levels were increased in the SN in animal models of PD, suggesting that CSF-1 is the predominant factor in PD.…”

“…We found that samples from PD patients had higher gene expression of CSF1R and significantly higher CSF-1 gene expression compared to age-matched controls, whereas IL-34 was not different between the groups (Figure 1). 44,45 We observed increased CSF-1 mRNA levels in the brains of PD patients compared to age-matched controls ( Figure 1B), whereas we found no difference in IL-34 mRNA levels ( Figure 1C). We tested this hypothesis by utilizing an LPS inflammation model and an acute MPTP neurotoxicity model.…”

Fibrocytes, Wound Healing, and Corneal Fibrosis

“…47 IL-34 is a newly identified cytokine that activates the colony-stimulating factor-1 receptor (CSF-1R). 48 Galligan and Fish 49 show that in vitro fibrocyte precursors treated with IL-34 induce the proliferation of fibrocytes-mediated by the…”

Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL‐34, and SCF in amyotrophic lateral sclerosis

“…CSF1 and IL‐34 are the two endogenous cognate ligands of CSF‐1R, which upon activation stimulates monocyte/macrophage differentiation pattern and the acquisition of a phagocytic phenotype (Boulakirba et al, ). On the other hand, SCF is the ligand of c‐Kit, which in peripheral tissues is mainly expressed in mast cells (Iemura, Tsai, Ando, Wershil, & Galli, ).…”