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Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells
Open accessAbstract
Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4+CD8−Foxp3+ thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (∼70%) of Foxp3+ T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-β expressed Helios. Ag-specific Foxp3+ T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3+ Treg cells are generated extrathymically.
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“In mice, high expression of Helios and low expression of Neuropilin-1 (Nrp-1) has been proposed to discriminate between thymus Treg and peripherally-induced Tregs [364, 365]”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [364]
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“Yet, Helios, Nrp-1 or ROR-γt are widely accepted for the discrimination of tTreg and pTreg cells under homeostatic conditions [364-366, 437-440].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [364]
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Metadata
- Authors
- Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., & Shevach, E. M.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Immunology
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-01
- Volume
- 184
- Issue
- 7
- Pages
- 3433-3441
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3725574
- OpenAlex
- W2111329034
- Cited by
- 1,382
- References
- 47
- Citations by year
- 2026: 44 · 2025: 55 · 2024: 63 · 2023: 50 · 2022: 70 · 2021: 57 · 2020: 70 · 2019: 84 · 2018: 82 · 2017: 74 · 2016: 97 · 2015: 119 · 2014: 110 · 2013: 144 · 2012: 129
- FWCI
- 55.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- 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
- Helios, Foxp3+ regulatory T cells, T cell development, double-negative thymocytes, TGF-beta
- MeSH terms
- Animals, Cell Differentiation, Cell Separation, DNA-Binding Proteins, Female, Flow Cytometry, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Spleen, Thymus Gland, Transcription Factors, T-Lymphocyte Subsets, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Mice, Ikaros Transcription Factor, Forkhead Transcription Factors
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