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Helios Controls a Limited Subset of Regulatory T Cell Functions
Open accessAbstract
A subpopulation (60–70%) of Foxp3+ regulatory T cells (Tregs) in both mouse and man expresses the transcription factor Helios, but its role in Treg function is still unknown. We generated Treg-specific Helios-deficient mice to examine the function of Helios in Tregs. We show that the selective deletion of Helios in Tregs leads to slow, progressive systemic immune activation, hypergammaglobulinemia, and enhanced germinal center formation in the absence of organ-specific autoimmunity. Helios-deficient Treg suppressor function was normal in vitro, as well as in an in vivo inflammatory bowel disease model. However, Helios-deficient Tregs failed to control the expansion of pathogenic T cells derived from scurfy mice, failed to mediate T follicular regulatory cell function, and failed to control both T follicular helper cell and Th1 effector cell responses. In competitive settings, Helios-deficient Tregs, particularly effector Tregs, were at a disadvantage, indicating that Helios regulates effector Treg fitness. Thus, we demonstrate that Helios controls certain aspects of Treg-suppressive function, differentiation, and survival.
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“Notably, the preferential Helios degrader ALV2 destabilized the anergic phenotype of regulatory Tregs, consistent with previously reported phenotypes of Ikzf2−/− Tregs5,6,29, demonstrating that acute pharmacological degradation of Helios recapitulates the phenotype of genetic loss of Ikzf2 in Tregs.”
From Acute pharmacological degradation of Helios destabilizes regulatory T cells (2021) · cites this paper as [29]
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Metadata
- Authors
- Sebastian, M., Lopez-Ocasio, M., Metidji, A., Rieder, S. A., Shevach, E. M., & Thornton, A. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Shevach, Ethan M
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-01-01
- Volume
- 196
- Issue
- 1
- Pages
- 144-155
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4685018
- OpenAlex
- W2178643122
- Cited by
- 172
- References
- 46
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 6 · 2023: 19 · 2022: 10 · 2021: 22 · 2020: 14 · 2019: 29 · 2018: 22 · 2017: 13 · 2016: 13
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (Z01AI000959)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- Helios, regulatory T cells, Foxp3, Treg suppressive function, systemic immune activation, hypergammaglobulinemia, germinal center formation, inflammatory bowel disease, scurfy mice, follicular regulatory T cells, T follicular helper cells
- MeSH terms
- Animals, Autoimmune Diseases, Cell Differentiation, Disease Models, Animal, DNA-Binding Proteins, Female, Hypergammaglobulinemia, Male, Mice, Inbred C57BL, Transcription Factors, Inflammatory Bowel Diseases, Autoimmunity, Mice, Knockout, Th1 Cells, Germinal Center, T-Lymphocytes, Regulatory, Mice, Ikaros Transcription Factor, Forkhead Transcription Factors
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