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Updated: Jan 12, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
TET3-overexpressing macrophages are a unifying pathogenic feature with therapeutic potential in chronic inflammatory
Abstract:
Increased activation of the NLRP3 inflammasome in immune cells, including macrophages, has been implicated in the pathogenesis of multiple chronic inflammatory diseases. Targeted depletion of macrophages has been explored as a cross-disease therapeutic strategy, but without subtype-specific markers, this strategy risks elimination of macrophages with homeostatic functions. In this study, Liu et al. identified a subpopulation of pathogenic macrophages, referred to as Toe-Macs, which are characterized by overexpression of the DNA demethylase TET3 in metabolic dysfunction-associated steatohepatitis (MASH), non-small cell lung cancer (NSCLC), and endometriosis. When induced into the disease microenvironment, Toe-Macs produced proinflammatory cytokines and chemokines. Selective elimination of Toe-Macs attenuated disease progression without any discernible side effects in mouse models of MASH and NSCLC. These findings highlight the role of Toe-Macs in the pathogenesis of chronic inflammatory diseases and provide a rationale for exploring TET3 as a therapeutic target.
Insights
Researchers identified pathogenic macrophages, termed Toe-Macs, overexpressing TET3 in chronic inflammatory diseases like MASH and NSCLC. Selective elimination of these Toe-Macs reduced disease progression, suggesting TET3 as a potential therapeutic target.
Area of Science:
- Immunology
- Cell Biology
- Pathogenesis of Chronic Inflammatory Diseases
Background:
- NLRP3 inflammasome activation in macrophages contributes to chronic inflammatory diseases.
- Targeted macrophage depletion is a potential therapy but lacks specificity.
- Homeostatic macrophage functions may be compromised by non-specific depletion strategies.
Purpose of the Study:
- Identify specific macrophage subtypes involved in chronic inflammation.
- Characterize pathogenic macrophages and their molecular markers.
- Evaluate the therapeutic potential of targeting specific macrophage populations.
Main Methods:
- Identification of macrophage subpopulations based on gene expression.
- Analysis of TET3 overexpression in disease models (MASH, NSCLC, endometriosis).
- Selective depletion of identified macrophage subtypes in preclinical models.
Main Results:
- A pathogenic macrophage subset, Toe-Macs, overexpressing TET3 was identified.
- Toe-Macs were found in metabolic dysfunction-associated steatohepatitis (MASH), non-small cell lung cancer (NSCLC), and endometriosis.
- Selective elimination of Toe-Macs ameliorated disease progression in MASH and NSCLC mouse models without side effects.
Conclusions:
- Toe-Macs play a significant role in the pathogenesis of chronic inflammatory diseases.
- TET3 is a potential therapeutic target for diseases involving Toe-Macs.
- Targeting specific pathogenic macrophage subtypes offers a promising therapeutic strategy.
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