MINI REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1621328
This article is part of the Research TopicThe Role of Ubiquitin Ligases in Regulating Immune Cell Functions: Cbl and BeyondView all 3 articles
Ubiquitination in Macrophage Plasticity: From Inflammatory to Immunometabolic Pathways
Provisionally accepted
- Karolinska Institutet (KI), Solna, Sweden
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Macrophages are highly plastic innate immune cells whose polarization and effector functions are tightly linked to their metabolic programs. Ubiquitination, the post-translational modification that attaches ubiquitin chains to target proteins, plays a crucial role in regulating macrophage immunometabolism and phenotype transitions. In this mini-review, we summarize the current understanding of ubiquitin-dependent mechanisms that modulate macrophage polarization. We discuss how E3 ubiquitin ligases and deubiquitinases regulate key metabolic and signaling pathways, balancing pro-inflammatory and immunosuppressive states. Additionally, we describe the pathophysiological consequences of dysregulated ubiquitin-dependent control of macrophage polarization and its implications for disease. These insights underscore the importance of ubiquitination as a central modulator of macrophage function and its potential as a therapeutic target for controlling immunity in infections, inflammation, and cancer.
Keywords: macrophage, polarization, Ubiquitination, Immunometabolism, Inflammation
Received: 02 May 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Liu and Paolino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Magdalena Paolino, Karolinska Institutet (KI), Solna, Sweden
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