Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages.
HIF
IL-4
macrophage
metabolism
metallothionein 3
polarization
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
25 06 2019
25 06 2019
Historique:
received:
16
01
2019
revised:
01
05
2019
accepted:
22
05
2019
entrez:
27
6
2019
pubmed:
27
6
2019
medline:
31
7
2020
Statut:
ppublish
Résumé
Alternatively activated (M2) macrophages promote wound healing but weaken antimicrobial defenses. The mechanisms that enforce macrophage divergence and dictate the phenotypic and metabolic characteristics of M2 macrophages remain elusive. We show that alternative activation with interleukin (IL)-4 induces expression of metallothionein 3 (MT3) that regulates macrophage polarization and function. MT3 was requisite for metabolic reprograming in IL-4-stimulated macrophages or M(IL-4) macrophages to promote mitochondrial respiration and suppress glycolysis. MT3 fostered an M(IL-4) phenotype, suppressed hypoxia inducible factor (HIF)1α activation, and thwarted the emergence of a proinflammatory M1 program in macrophages. MT3 deficiency augmented macrophage plasticity, resulting in enhanced interferon γ (IFNγ) responsiveness and a dampened M(IL-4) phenotype. Thus, MT3 programs the phenotype and metabolic fate of M(IL-4) macrophages.
Identifiants
pubmed: 31242420
pii: S2211-1247(19)30732-6
doi: 10.1016/j.celrep.2019.05.093
pmc: PMC6664296
mid: NIHMS1532877
pii:
doi:
Substances chimiques
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Il4 protein, mouse
0
Metallothionein 3
0
Mt3 protein, mouse
0
Nerve Tissue Proteins
0
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3873-3886.e7Subventions
Organisme : NIAID NIH HHS
ID : R01 AI133797
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 19CDA34770022
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 15POST25700182
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES006096
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI106269
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099222
Pays : United States
Informations de copyright
Published by Elsevier Inc.