ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Myeloid-T cell proximity is prominent in healthy pregnancies with extreme fetal-maternal HLA incompatibility.iScience · 2026Article
- FCRL3 is an immunoregulatory receptor that restrains the activation of human memory T lymphocytes.The Journal of experimental medicine · 2026Article
- 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.Genome biology · 2025Article
- Two subsets of regulatory CD8iScience · 2025Article
- Targeting Impaired Type I Interferon-IL-27 Signaling Rescues T Regulatory Cell Suppressive Function in Relapsing-Remitting Multiple Sclerosis.bioRxiv : the preprint server for biology · 2025Article
- High-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells.Molecular therapy. Methods & clinical development · 2024Article
- KIR2DL2/DL3+NKs and Helios+Tregs in Peripheral Blood Predict Nivolumab Response in Patients with Metastatic Renal Cell Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- High affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells.bioRxiv : the preprint server for biology · 2024Article
- Pathogenic role of different phenotypes of immune cells in airway allergic diseases: a study based on Mendelian randomization.Frontiers in immunology · 2024Article
- A sex-biased imbalance between Tfr, Tph, and atypical B cells determines antibody responses in COVID-19 patients.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Treg in inborn errors of immunity: gaps, knowns and future perspectives.Frontiers in immunology · 2023Review
- The interplay between the microbiota, diet and T regulatory cells in the preservation of the gut barrier in inflammatory bowel disease.Frontiers in microbiology · 2023Review
- Non-coding RNA in tumor-infiltrating regulatory T cells formation and associated immunotherapy.Frontiers in immunology · 2023Review
- Regulatory T cells infiltrate the tumor-induced tertiary lymphoïd structures and are associated with poor clinical outcome in NSCLC.Communications biology · 2022Article
- Recent highlights in the immunomodulatory aspects of Treg cell-derived extracellular vesicles: special emphasis on autoimmune diseases and transplantation.Cell & bioscience · 2022Review
- Improving the Efficacy of Regulatory T Cell Therapy.Clinical reviews in allergy & immunology · 2022Review
- The Association between Regulatory T Cell Subpopulations and Severe Pneumonia Post Renal Transplantation.Journal of immunology research · 2022Article
- Co-Expression of TIGIT and Helios Marks Immunosenescent CD8Frontiers in immunology · 2022Article
- Untangling the Knots of Regulatory T Cell Therapy in Solid Organ Transplantation.Frontiers in immunology · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Two distinct subsets of CD4(+)Foxp3(+) regulatory T (Treg) cells have been described based on the differential expression of Helios, a transcription factor of the Ikaros family. Efforts to understand the origin and biological roles of these Treg populations in regulating immune responses have, however, been hindered by the lack of reliable surface markers to distinguish and isolate them for subsequent functional studies. Using a single-cell cloning strategy coupled with microarray analysis of different Treg functional subsets in humans, we identify the mRNA and protein expression of TIGIT and FCRL3 as a novel surface marker combination that distinguishes Helios(+)FOXP3(+) from Helios(-)FOXP3(+) memory cells. Unlike conventional markers that are modulated on conventional T cells upon activation, we show that the TIGIT/FCRL3 combination allows reliable identification of Helios(+) Treg cells even in highly activated conditions in vitro as well as in PBMCs of autoimmune patients. We also demonstrate that the Helios(-)FOXP3(+) Treg subpopulation harbors a larger proportion of nonsuppressive clones compared with the Helios(+)FOXP3(+) cell subset, which is highly enriched for suppressive clones. Moreover, we find that Helios(-) cells are exclusively responsible for the productions of the inflammatory cytokines IFN-γ, IL-2, and IL-17 in FOXP3(+) cells ex vivo, highlighting important functional differences between Helios(+) and Helios(-) Treg cells. Thus, we identify novel surface markers for the consistent identification and isolation of Helios(+) and Helios(-) memory Treg cells in health and disease, and we further reveal functional differences between these two populations. These new markers should facilitate further elucidation of the functional roles of Helios-based Treg heterogeneity.
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Registered trials
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.