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REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1535823
This article is part of the Research Topic Modulation of Pro-Inflammatory Signaling by Interferons View all 5 articles
Interferon Regulatory Factor 5 (IRF 5): A Potential Target for Therapeutic Intervention in Inflammatory Diseases
Provisionally accepted
Xinyuan Yu 1
Ata Ur Rehman 2 Lihong Dang 2
Xu Zhang 1
Jia Liu 3
Xiaoxing Xiong 1 Gang Chen 1*
Zhihong Jian 1*- 1 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- 2 Duke University Medical Center, Duke University, Durham, United States
- 3 Department of Neuroscience, School of Medicine, Yale University, New Haven, Connecticut, United States
Interferon regulatory factor 5 (IRF5) is a critical transcription factor in the IRF family, playing a pivotal role in modulating immune responses, particularly within the innate immune system. IRF5 regulates the expression of type I interferons (IFNs), proinflammatory cytokines, and other immune-related genes, essential for effective host defense against infections and immune surveillance. Its functions, however, are diverse and highly context-dependent, adapting to different immune challenges and tissue environments. Studies have demonstrated that dysregulated IRF5 activation contributes to the pathogenesis of numerous diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This dysregulation underscores the dual role of IRF5, both in immune protection and in driving pathological inflammation.Given its significant involvement in both physiological and pathological processes, IRF5 presents a promising therapeutic target for managing diseases characterized by excessive inflammation and immune dysregulation. However, developing effective molecules to specifically modulate the IRF5 pathway remains challenging, with limited therapeutic agents available for clinical application. In this review, we examine the diverse roles of IRF5 in various disease contexts, the mechanisms by which IRF5 contributes to disease progression, and the potential therapeutic strategies targeting IRF5. Additionally, we discuss potential complications and risks associated with IRF5-targeted therapies, including the balance between dampening pathological inflammation and preserving essential immune functions. This exploration highlights both the therapeutic potential and the complexity of modulating IRF5 activity in clinical settings.
Keywords: IRF5, tumorigenesis, Inflammatory diseases, Cytokines, Autoimmune Diseases
Received: 27 Nov 2024; Accepted: 06 Mar 2025.
Copyright: © 2025 Yu, Rehman, Dang, Zhang, Liu, Xiong, Chen and Jian. 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:
Gang Chen, Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Zhihong Jian, Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.