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

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons201435

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

External Resource

https://www.sciencedirect.com/science/article/pii/S1074761315000801
(Copyright transfer agreement)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

Jha et al..pdf
(Publisher version), 4MB

Supplementary Material (public)

There is no public supplementary material available

Citation

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.

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

Abstract

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.