Cited by 172T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCancer Immunotherapy and Biomarkers

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Helios Controls a Limited Subset of Regulatory T Cell Functions

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Sebastian, Mathew, Lopez-Ocasio, Maria, Metidji, Amina, Rieder, Sadiye Amcaoglu, Shevach, Ethan M, Thornton, Angela M·2016·The Journal of Immunology

DOI 10.4049/jimmunol.1501704PMC PMC4685018

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Abstract

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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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
ORCID: Sebastian, Mathew
Lopez-Ocasio, Maria
Metidji, Amina
Shevach, Ethan M
Thornton, Angela 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
DOI: 10.4049/jimmunol.1501704
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
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
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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Helios Controls a Limited Subset of Regulatory T Cell Functions

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