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

Abstract : Interleukin-34 (IL-34) is a newly-discovered homodimeric cytokine that regulates, like Macrophage Colony-Stimulating Factor (M-CSF), the differentiation of the myeloid lineage through M-CSF receptor (M-CSFR) signaling pathways. To date, both cytokines have been considered as competitive cytokines with regard to the M-CSFR. The aim of the present work was to study the functional relationships of these cytokines on cells expressing the M-CSFR. We demonstrate that simultaneous addition of M-CSF and IL-34 led to a specific activation pattern on the M-CSFR, with higher phosphorylation of the tyrosine residues at low concentrations. Similarly, both cytokines showed an additive effect on cellular proliferation or viability. In addition, BIAcore experiments demonstrated that M-CSF binds to IL-34, and molecular docking studies predicted the formation of a heteromeric M-CSF/IL-34 cytokine. A proximity ligation assay confirmed this interaction between the cytokines. Finally, co-expression of the M-CSFR and its ligands differentially regulated M-CSFR trafficking into the cell. This study establishes a new foundation for the understanding of the functional relationship between IL-34 and M-CSF, and gives a new vision for the development of therapeutic approaches targeting the IL-34/M-CSF/M-CSFR axis.
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Cytokine, Elsevier, 2015, 76 (2), pp.170 - 181. 〈10.1016/j.cyto.2015.05.029〉
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Soumis le : mercredi 22 novembre 2017 - 15:39:02
Dernière modification le : jeudi 5 avril 2018 - 10:37:01

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Aude Segaliny, Régis Brion, Bénédicte Brulin, Mike Maillasson, Céline Charrier, et al.. IL-34 and M-CSF form a novel heteromeric cytokine and regulate the M-CSF receptor activation and localization: IL-34/M-CSF: a new heteromeric cytokine. Cytokine, Elsevier, 2015, 76 (2), pp.170 - 181. 〈10.1016/j.cyto.2015.05.029〉. 〈inserm-01644778〉

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