The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1
Open accessAbstract
Significance: Treg cells suppress excessive and aberrant immune responses. Impaired function or homeostasis of Treg cells would induce severe autoimmune and inflammatory diseases. Forkhead box P3 (FOXP3), as a master regulator of Treg cells, forms a large complex with other binding factors to modulate Treg-cell function subtly in pathological and physiological conditions. We identified that Deleted in breast cancer 1 (DBC1) is an essential subunit of the FOXP3 complex in human CD4 + Treg cells. Our results show that the inflammatory cytokines TNF-α or IL-6 trigger FOXP3 degradation, whereas downregulation of DBC1 expression prevents FOXP3 degradation and maintains Treg-cell function under inflammatory stimuli in vitro and in vivo. These findings unveil a previously unidentified pathway for therapeutically modulating FOXP3 + Treg-cell stability under inflammation.
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“Notably, TNF-α has also been shown to directly promote FOXP3 degradation in Tregs (Gao et al. 2015), providing mechanistic insight into how inflammatory cytokines destabilize Treg identity and reinforcing the conclusion that TNF-α-mediated signals contribute to the loss of immunoregulatory balance during MASH.”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Gao et al. 2015
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Cites
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The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer
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Transient expression of FOXP3 in human activated nonregulatory CD4 + T cells
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Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease
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Metadata
- Authors
- Gao, Y., Tang, J., Chen, W., Li, Q., Nie, J., Lin, F., Wu, Q., Chen, Z., Gao, Z., Fan, H., Tsun, A., Shen, J., Chen, G., Liu, Z., Lou, Z., Olsen, N. J., Zheng, S. G., & Li, B.
- Affiliations
- Sun Yat-sen University (CN)
- Tongji University (CN)
- Pennsylvania State University (US)
- Chinese Academy of Sciences (CN)
- Anhui Medical University (CN)
- Mayo Clinic (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-06-09
- Volume
- 112
- Issue
- 25
- Pages
- E3246-54
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4485127
- OpenAlex
- W1503625166
- Cited by
- 140
- References
- 43
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 6 · 2023: 9 · 2022: 12 · 2021: 18 · 2020: 27 · 2019: 20 · 2018: 11 · 2017: 7 · 2016: 4 · 2015: 1
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR059103)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- Foxp3, regulatory T cells, DBC1, inflammation, protein stability, protein degradation, experimental autoimmune encephalomyelitis, colitis, immune homeostasis, inflammatory diseases
- MeSH terms
- Animals, Encephalomyelitis, Autoimmune, Experimental, Mice, Inbred C57BL, Adaptor Proteins, Signal Transducing, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors
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