Imperial College London
Alternate

PROFESSOR H. TERENCE COOK

Faculty of Medicine, Department of Immunology and Inflammation

Emeritus Professor
 
 
 
//

Contact

 

+44 (0)20 3313 2009t.h.cook

 
 
//

Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
//

Location

 

9N9Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pereira:2019:10.1016/j.celrep.2019.06.039,
author = {Pereira, M and Chen, T-D and Buang, N and Olona, A and Ko, J-H and Prendecki, M and Costa, ASH and Nikitopoulou, E and Tronci, L and Pusey, CD and Cook, HT and McAdoo, SP and Frezza, C and Behmoaras, J},
doi = {10.1016/j.celrep.2019.06.039},
journal = {Cell Reports},
pages = {498--511.e5},
title = {Acute iron deprivation reprograms human macrophage metabolism and reduces inflammation in vivo},
url = {http://dx.doi.org/10.1016/j.celrep.2019.06.039},
volume = {28},
year = {2019}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Iron is an essential metal for fine-tuning the innate immune response through macrophage function. An integrative view of transcriptional and metabolic responses generated from iron perturbation in macrophages is lacking. Here we induced acute iron chelation in primary human macrophages and measured their transcriptional and metabolic responses by integrating RNA-sequencing and stable isotope tracing. We show that acute iron deprivation causes an anti-proliferative Warburg transcriptome characterized by an ATF4-dependent signature. Metabolically, iron-deprived human macrophages show an inhibition of oxidative phosphorylation and a concomitant increase in glycolysis, a large increase in glucosederived citrate pools associated with lipid droplet accumulation and modest levels of itaconate production. LPS polarization increases itaconate/succinate ratio and decreases pro-inflammatory cytokine production in iron-deprived macrophages. Acute iron deprivation reduces the severity of macrophage-dependent crescentic glomerulonephritis by limiting glomerular cell proliferation and inducing lipid accumulation in the renal cortex, phenocopying partly the iron-driven metabolic and transcriptional responses. These results suggest that acute iron deprivation has in vivo protective effects, by causing an antiinflammatory immuno-metabolic switch in macrophages.
AU  - Pereira,M
AU  - Chen,T-D
AU  - Buang,N
AU  - Olona,A
AU  - Ko,J-H
AU  - Prendecki,M
AU  - Costa,ASH
AU  - Nikitopoulou,E
AU  - Tronci,L
AU  - Pusey,CD
AU  - Cook,HT
AU  - McAdoo,SP
AU  - Frezza,C
AU  - Behmoaras,J
DO  - 10.1016/j.celrep.2019.06.039
EP  - 511
PY  - 2019///
SN  - 2211-1247
SP  - 498
TI  - Acute iron deprivation reprograms human macrophage metabolism and reduces inflammation in vivo
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2019.06.039
UR  - http://hdl.handle.net/10044/1/70660
VL  - 28
ER  -
Download