Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages.

Abstract:

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Chowdhury D,Alrefai H,Landero Figueroa JA,Candor K,Porollo A,Fecher R,Divanovic S,Deepe GS Jr,Subramanian Vignesh K

doi

10.1016/j.celrep.2019.05.093

subject

Has Abstract

pub_date

2019-06-25 00:00:00

pages

3873-3886.e7

issue

13

issn

2211-1247

pii

S2211-1247(19)30732-6

journal_volume

27

pub_type

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