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Editorial
. 2023 Nov 1;133(21):e174540.
doi: 10.1172/JCI174540.

GLUT3 regulates alternative macrophage signaling through a glucose transport-independent role

Peng Zhang, Jason Miska, Amy B Heimberger
Editorial

GLUT3 regulates alternative macrophage signaling through a glucose transport-independent role

Peng Zhang et al. J Clin Invest. .

Abstract

Macrophages are key mediators of innate immunity whose functional state can be regulated by glucose transporters. Although abundantly expressed in macrophages, the specific function of GLUT3, an isoform of facilitative glucose transporters, has not been clearly established. In this issue of the JCI, Dong-Min Yu and colleagues identify an alternative role for GLUT3 in promoting M2 macrophage polarization. The authors demonstrated that GLUT3 was upregulated upon M2 stimulation and was required for efficient alternative macrophage polarization and function. They further showed that GLUT3-induced M2 polarization was independent of glucose transport and functioned through Ras-mediated regulation of IL-4R endocytosis and IL-4/STAT6 activation. These findings may guide the development of macrophage-targeted treatments.

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Conflict of interest statement

Conflict of interest: ABH serves on the advisory board of Caris Life Sciences and the WCG Oncology Advisory Board, and is supported by research grants from Alnylam and AbbVie. She additionally has active granted patents titled “miRNA for treating cancer and for use with adoptive immunotherapies” (no. 9,675,633) and “Concurrent chemotherapy and immunotherapy” (no. 9,399,662), with a patent pending, “Low intensity ultrasound combination cancer therapies” (international applications PCT/US2022/019435 and US 63/158,642). PZ has pending patents “Cytotoxic lipid particles targeted to tumor-associated myeloid cells (TAMCs) and synergized with radiation therapy for treating glioblastoma” (NU2019-169; 17/089,563) and “Lipid nanoparticles and methods of using the same for treating cell proliferative diseases and disorders” (NU2022-151; 63/380,317).

Figures

Figure 1
Figure 1. GLUT3 induces M2 polarization of macrophages.
GLUT3-induced M2 polarization is glucose transport independent and functions through Ras-mediated regulation of IL-4R endocytosis and IL-4/STAT6 activation.
See this image and copyright information in PMC

Comment on

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