Network integration of parallel metabolomics and transcirptional data reveals 
metabolic modules that regulate macrophage polarization

Jha, A.K.; Huang, S.C.; Sergushichev, A.; Lampropoulo, V.; Ivanova , Y.; Loginicheva , E.; Chielewski, K.; Stewart, K.M.; Ashali, J.; Everts, B.; Pearce, E.J.; Driggers, E.M.; Artyomov, A.

doi:org/10.1016/j.immuni.2015.02.005

Datensatz

DATENSATZ AKTIONENEXPORT

Zur Ablage hinzufügen

Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben

Zeitschriftenartikel

Network integration of parallel metabolomics and transcirptional data reveals metabolic modules that regulate macrophage polarization

MPG-Autoren

/persons/resource/persons201435

Pearce, E.J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Externe Ressourcen

https://www.sciencedirect.com/science/article/pii/S1074761315000801
(Verlagsvertrag)

Volltexte (beschränkter Zugriff)

Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.

Volltexte (frei zugänglich)

Jha et al..pdf
(Verlagsversion), 4MB

Ergänzendes Material (frei zugänglich)

Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar

Zitation

Jha, A., Huang, S., Sergushichev, A., Lampropoulo, V., Ivanova, Y., Loginicheva, E., et al. (2015). Network integration of parallel metabolomics and transcirptional data reveals metabolic modules that regulate macrophage polarization. Immunity, 42, 419-430. doi:org/10.1016/j.immuni.2015.02.005.

Zitierlink: https://hdl.handle.net/21.11116/0000-0006-C064-0

Zusammenfassung

Macrophage polarization involves a coordinated metabolic and transcriptional rewiring that is only partially understood. By using an integrated high-throughput transcriptional-metabolic profiling and analysis pipeline, we characterized systemic changes during murine macrophage M1 and M2 polarization. M2 polarization was found to activate glutamine catabolism and UDP-GlcNAc-associated modules. Correspondingly, glutamine deprivation or inhibition of N-glycosylation decreased M2 polarization and production of chemokine CCL22. In M1 macrophages, we identified a metabolic break at Idh, the enzyme that converts isocitrate to alpha-ketoglutarate, providing mechanistic explanation for TCA cycle fragmentation. 13C-tracer studies suggested the presence of an active variant of the aspartate-arginosuccinate shunt that compensated for this break. Consistently, inhibition of aspartate-aminotransferase, a key enzyme of the shunt, inhibited nitric oxide and interleukin-6 production in M1 macrophages, while promoting mitochondrial respiration. This systems approach provides a highly integrated picture of the physiological modules supporting macrophage polarization, identifying potential pharmacologic control points for both macrophage phenotypes.