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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): 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
Zeitschrift: Blood Advances
Jahr der Veröffentlichung: 2017
Band: 1
Heftnummer: 14
Seitenbereich: 947-960
ISSN: 2473-9529
eISSN: 2476-9537


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.


FAU-Autoren / FAU-Herausgeber

Bogdan, Christian Prof. Dr.
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Schleicher, Ulrike PD Dr.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene


Autor(en) der externen Einrichtung(en)
Julius-Maximilians-Universität Würzburg
Philipps-Universität Marburg
Universität Regensburg
Universitätsklinikum Würzburg


Zitierweisen

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.

BibTeX: 

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