Novel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function

Ribechini E, Hutchinson JA, Hergovits S, Heuer M, Lucas J, Schleicher U, Garrote ALJ, Potter SJ, Riquelme P, Brackmann H, Muller N, Raifer H, Berberich I, Huber M, Beilhack A, Lohoff M, Bogdan C, Eyrich M, Hermanns HM, Geissler EK, Lutz MB (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Blood Advances American Society of Hematology

Book Volume: 1

Pages Range: 947-960

Journal Issue: 14

DOI: 10.1182/bloodadvances.2017006858

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh and human CD14+ monocytes that disables their inflammatory functions and promotes their conversion into suppressor cells. This 2-step licensing of monocytes requires activation of the AKT/mTOR/mTORC1 signaling cascade by GM-CSF followed by signaling through the interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway. Only licensing-dependent adaptations in Toll-like receptor/inflammasome, IFN-γR, and phosphatidylinositol 3-kinase/AKT/mTOR signaling lead to stabilized expression of inducible nitric oxide synthase by mouse and indoleamine 2,3-dioxygenase (IDO) by human monocytes, which accounts for their suppressor activity. This study suggests various myeloid cells with characteristics similar to those described for monocytic myeloid-derived suppressor cells, Mreg, or suppressor macrophages may arise from licensed monocytes. Markers of GM-CSF-driven monocyte licensing, including p-Akt, p-mTOR, and p-S6, distinguish inflammatory monocytes from potentially suppressive monocytes in peripheral blood of patients with high-grade glioma.

Authors with CRIS profile

Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universität Regensburg DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Philipps-Universität Marburg DE Germany (DE)

How to cite

APA:

Ribechini, E., Hutchinson, J.A., Hergovits, S., Heuer, M., Lucas, J., Schleicher, U.,... Lutz, M.B. (2017). Novel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function. Blood Advances, 1(14), 947-960. https://dx.doi.org/10.1182/bloodadvances.2017006858

MLA:

Ribechini, Eliana, et al. "Novel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function." Blood Advances 1.14 (2017): 947-960.

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