REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1652398
This article is part of the Research TopicCommunity Series in Immune Tolerance Dual Role: Advancements in Cancer and Autoimmune Diseases, Volume IIView all articles
Super-Enhancers in Immune System Regulation: Mechanisms, Pathological Reprogramming, and Therapeutic Opportunities
Provisionally accepted
- 1The Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
- 2Shenzhen Bao'an Chinese Medicine Hospital, Shenzhen, China
- 3The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Super-enhancers (SEs) are dynamic chromatin structures that function as epigenetic hubs, orchestrating cell-type-specific transcriptional programs crucial for immune cell differentiation, functional specialization, and adaptive responses. These enhancer clusters integrate transcription factor (TF) networks, chromatin-modifying signals, and three-dimensional genome organization to govern lineage commitment, effector function acquisition, and metabolic reprogramming while enabling plasticity in response to environmental cues. SEs exhibit spatiotemporal regulatory properties, such as chromatin looping, phase-separated condensate formation, and stimulus-driven enhancer-promoter rewiring, all of which stabilize transcriptional outputs vital for immune homeostasis. Pathological dysregulation of SEs disrupts immune tolerance and amplifies aberrant transcriptional circuits, contributing to immunemediated diseases marked by chronic inflammation, autoimmunity, or malignancy. Emerging therapeutic strategies targeting SE-associated components show promise in dismantling pathogenic enhancer networks through CRISPR-based editing, small-molecule inhibitors, and proteolysis-targeting chimeras(PROTACs). However, challenges remain in achieving therapeutic specificity amidst the dynamic reorganization of SEs and ensuring cell-type-selective delivery. By providing insights into SEdriven chromatin dynamics and transcriptional control in health and disease, this review focuses on two central questions: whether SEs causally drive immune cell fate decisions, and how they function within shared core transcriptional regulatory networks across cancer, infection, and autoimmune diseases.Future advances in multi-omics profiling, single-cell resolution analyses, and combinatorial therapeutic strategies will be critical for translating SE biology into precision interventions that restore immune equilibrium in dysregulated conditions.
Keywords: SES, Immune System, Transcription Regulation, Cell signaling, Pathogenesis
Received: 23 Jun 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 Lai, Li, Tang, Luo, Wu, Huang and Li. 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:
Bihui Huang, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
Hang Li, The Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 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.