IL-34 and M-CSF form a novel heteromeric cytokine and regulate the M-CSF receptor activation and localization.

摘要: Interleukin-34 (IL-34) is a newly-discovered homodimeric cytokine that regulates, like Macrophage Colony-Stimulating Factor (M-CSF), the differentiation of myeloid lineage through M-CSF receptor (M-CSFR) signaling pathways. To date, both cytokines have been considered as competitive with regard to M-CSFR. The aim present work was study functional relationships these on cells expressing We demonstrate simultaneous addition and IL-34 led specific activation pattern M-CSFR, higher phosphorylation tyrosine residues at low concentrations. Similarly, showed an additive effect cellular proliferation or viability. In addition, BIAcore experiments demonstrated binds IL-34, molecular docking studies predicted formation heteromeric M-CSF/IL-34 cytokine. A proximity ligation assay confirmed this interaction between cytokines. Finally, co-expression M-CSFR its ligands differentially regulated trafficking into cell. This establishes new foundation for understanding relationship M-CSF, gives vision development therapeutic approaches targeting IL-34/M-CSF/M-CSFR axis.