REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1667053
This article is part of the Research TopicInterdisciplinary Innovations in CAR T-Cell Therapy for Autoimmune and Cancer TreatmentView all 5 articles
Opportunities and challenges harnessing antigen-specific CD4+ regulatory T cells (Tregs) in inflammatory bowel disease (IBD)
Provisionally accepted
- 1Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
- 2Universitatsklinikum Wurzburg Klinik und Poliklinik fur Allgemein- Viszeral- Transplantations- Gefas- und Kinderchirurgie, Würzburg, Germany
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
Inflammatory bowel diseases (IBD), including Crohn´s disease (CD) and ulcerative colitis (UC) remain highly prevalent and are associated with a reduced quality of life in affected patients. The pathophysiology of IBD is multifactorial since genetic predisposition, altered immune function, changes in intestinal microbiota, environmental factors, and loss of intestinal barrier function together induce disease manifestation. A critical key factor is the dysregulation of the immune system which explains that all medical therapeutic approaches target the immune response. However, the success of these therapies is limited and associated with severe side effects which demonstrates the need for novel therapeutic approaches. Previous research demonstrated that CD4+ regulatory T (Treg) cells are important regulators of intestinal homeostasis but are reduced in number and function relative to effector T cells in IBD. This led to the concept that genetically engineered, antigen-specific Tregs may represent a promising strategy to address immune dysregulation in IBD. Due to their antigen specificity, chimeric antigen receptors (CARs) enable additional target-dependent activation and migration of Tregs at disease sites. Chimeric antigen receptors (CARs) permit specific guidance to the effector site, i.e. the site of disease. While CARs receptors are increasingly established for the generation of antigen-specificity for T cell therapies in cancer, the implementation of CARs for IBD is in a preliminary state. Nonetheless, CAR constructs specific to circulating carcinoembryonic antigen (CEA), flagellin, or IL23R have been developed recently for potential application in IBD. Based on these novel developments, this review will discuss the role of Tregs in IBD disorders and present the current state of CAR Treg models.
Keywords: Regulatory T Cell, CAR receptor, Inflammatory Bowel Diseases, Flagellin- specific CAR, IL23R-CAR, cell therapy, Immunotherapy
Received: 16 Jul 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Kümmel, Schlegel and Wagner. 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: Johanna Claudia Wagner, wagner_j6@ukw.de
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.