Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation

A Achuthan; AD Cook; MC Lee; R Saleh; HW Khiew; MWN Chang; C Louis; AJ Fleetwood; DC Lacey; AD Christensen; AT Frye; PY Lam; H Kusano; K Nomura; N Steiner; I Förster; SL Nutt; M Olshansky; SJ Turner; JA Hamilton

Journal article

Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation

A Achuthan, AD Cook, MC Lee, R Saleh, HW Khiew, MWN Chang, C Louis, AJ Fleetwood, DC Lacey, AD Christensen, AT Frye, PY Lam, H Kusano, K Nomura, N Steiner, I Förster, SL Nutt, M Olshansky, SJ Turner, JA Hamilton

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2016

DOI: 10.1172/JCI87828

Abstract

Data from preclinical and clinical studies have demonstrated that granulocyte macrophage colony-stimulating factor (GMCSF) can function as a key proinflammatory cytokine. However, therapies that directly target GM-CSF function could lead to undesirable side effects, creating a need to delineate downstream pathways and mediators. In this work, we provide evidence that GM-CSF drives CCL17 production by acting through an IFN regulatory factor 4-dependent (IRF4-dependent) pathway in human monocytes, murine macrophages, and mice in vivo. In murine models of arthritis and pain, IRF4 regulated the formation of CCL17, which mediated the proinflammatory and algesic actions of GM-CSF. Mechanistically,..

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University of Melbourne Researchers

Adrian Achuthan Author

Kevin Lee Author

Reem Saleh Author

Andrew Fleetwood Author

Related Projects (1)

Cytokine regulation of inflammatory pain

What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated ..

Grants

Awarded by Australian Research Council

Funding Acknowledgements

AA and JAH were supported in part by a grant from GSK. AD Cook and JAH were supported by a grant (1043147) and JAH by a Senior Principal Research Fellowship from the National Health and Medical Research Council of Australia. AD Christensen was supported by a postdoc fellowship from Novo Nordisk A/S, Denmark. NS and IF were supported by the Deutsche Forschungsgemeinschaft (DFG) through SFB704. IF is a member of the DFG-funded cluster of excellence ImmunoSensation. SLN was supported by grants (361646, 575500 and 1054925) from the National Health and Medical Research Council of Australia. SJT was supported by grants (5671222 and 1003131) from the National Health and Medical Research Council of Australia and by an Australian Research Council Future Fellowship.