Evidence map›Paper›PMID 42694788›Full record

ReviewInternational journal of biological sciences2026

FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.

Yushuo Ren, Xiaohui Liu, Boya Wang, Haoyuan Yin, Jiatong Zhao, Shuzi Xin, Hongli Wang, Yuchen Zhang, Xinyue Liu, Jingyu Liu and 11 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Yushuo RenDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Xiaohui LiuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Boya WangKey laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Haoyuan YinDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Jiatong ZhaoDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Shuzi XinDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Hongli WangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Yuchen ZhangDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Xinyue LiuDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Jingyu LiuDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Rongxuan HuaLiver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Centre of Digestive Diseases, Beijing 100050, China.
Xiang TianDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Yuhang BianDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Sijin GuDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Haoxuan ZhangDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Tong WeiDepartment of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Lei GaoSchool of Intelligent Medical Engineering, School of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
Xin LuExperimental Centre for Morphological Research Platform, Capital Medical University, Beijing 100069, China.
Hongwei ShangExperimental Centre for Morphological Research Platform, Capital Medical University, Beijing 100069, China.
Han GaoDepartment of Clinical Laboratory, Aerospace Centre Hospital, 100049 Beijing, China.
Jingdong XuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulatory T cells (Tregs) maintain intestinal immune homeostasis, but their therapeutic potential is constrained by a fundamental paradox: the same plasticity that enables tissue repair renders FOXP3 vulnerable to degradation in chronic inflammation. Mechanistically, microbial metabolites (short-chain fatty acids, bile acids) and retinoic acid stabilize FOXP3 and induce RORγt⁺/GATA3⁺ Treg specialization. In contrast, inflammatory cytokines and succinate accumulation drive ER stress and post-translational FOXP3 degradation, leading to lineage instability in inflammatory bowel disease, colorectal cancer, and celiac disease. Current Tregs-based therapies-adoptive transfer, low-dose IL-2, CAR-Tregs, and microbiota consortia-have demonstrated safety profiles yet exhibit limited efficacy due to this inherent instability. Next-generation strategies therefore focus on actively stabilizing FOXP3 (e.g., gut-restricted HDAC inhibitors) and engineering exhaustion-resistant CAR-Tregs. Three questions remain for clinical translation: how to preserve Treg stability without compromising anti-tumor immunity; which biomarkers (succinate, TSDR methylation, FOXP3Δ2/FL ratio) predict response; and whether logic-gated CAR-Tregs can overcome exhaustion. Addressing these challenges will enable the development of precision Treg immunotherapy for intestinal diseases.

Indexed as

Forkhead Transcription FactorsIntestinal DiseasesT-Lymphocytes, RegulatoryAnimalsHumansForkhead Transcription FactorsFOXP3 protein, humanCAR-TregsColorectal cancerFOXP3FOXP3 stabilityImmunotherapyInflammatory bowel diseasemicrobiotaRegulatory T cells

Identifiers

PMID42694788
PMCPMC13541010

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.