ArticleBlood advances2020
Coexpression of FOXP3 and a Helios isoform enhances the effectiveness of human engineered regulatory T cells.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- A homozygous CTLA-4 variant causes CTLA-4 deficiency with severe immune dysregulation.Journal of human immunity · 2026Article
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- The role of miRNAs in the development of Super-Tregs as a potential therapy for neurodegenerative diseases.Frontiers in immunology · 2026Review
- Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs.PLoS computational biology · 2025Article
- Full-Length Transcriptome Sequencing Reveals Treg-Specific Isoform Expression upon Activation.International journal of molecular sciences · 2025Article
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- Tolerance Induction Strategies in Organ Transplantation: Current Status and Future Perspectives.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia.Cell reports · 2024Article
- Mini-Review: Tregs as a Tool for Therapy-Obvious and Non-Obvious Challenges and Solutions.Cells · 2024Review
- Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization.Haematologica · 2024Article
- Review
- A diet rich in fermentable fiber promotes robust changes in the intestinal microbiota, mitigates intestinal permeability, and attenuates autoimmune uveitis.Scientific reports · 2023Article
- Dexmedetomidine alleviates acute lung injury by promoting Tregs differentiation via activation of AMPK/SIRT1 pathway.Inflammopharmacology · 2023Article
- The small molecule inhibitor BX-795 uncouples IL-2 production from inhibition of Th2 inflammation and induces CD4Frontiers in immunology · 2023Article
- HELIOS-expressing human CD8 T cells exhibit limited effector functions.Frontiers in immunology · 2023Article
- Unlocking the potential of Tregs: innovations in CAR technology.Frontiers in molecular biosciences · 2023Review
- Regulatory T cells in rheumatoid arthritis: functions, development, regulation, and therapeutic potential.Cellular and molecular life sciences : CMLS · 2022Review
- Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease.Nature communications · 2022Article
- Improving the Efficacy of Regulatory T Cell Therapy.Clinical reviews in allergy & immunology · 2022Review
- Antimetabolite Drugs Exhibit Distinctive Immunomodulatory Mechanisms and Effects on the Intestinal Microbiota in Experimental Autoimmune Uveitis.Investigative ophthalmology & visual science · 2022Article
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Authors and funding
7 authors.
Funding
Abstract
Regulatory T cells (Tregs) are a subset of immune cells that suppress the immune response. Treg therapy for inflammatory diseases is being tested in the clinic, with moderate success. However, it is difficult to isolate and expand Tregs to sufficient numbers. Engineered Tregs (eTregs) can be generated in larger quantities by genetically manipulating conventional T cells to express FOXP3. These eTregs can suppress in vitro and in vivo but not as effectively as endogenous Tregs. We hypothesized that ectopic expression of the transcription factor Helios along with FOXP3 is required for optimal eTreg immunosuppression. To test this theory, we generated eTregs by retrovirally transducing total human T cells (CD4+ and CD8+) with FOXP3 alone or with each of the 2 predominant isoforms of Helios. Expression of both FOXP3 and the full-length isoform of Helios was required for eTreg-mediated disease delay in a xenogeneic graft-versus-host disease model. In vitro, this corresponded with superior suppressive function of FOXP3 and full-length Helios-expressing CD4+ and CD8+ eTregs. RNA sequencing showed that the addition of full-length Helios changed gene expression in cellular pathways and the Treg signature compared with FOXP3 alone or the other major Helios isoform. Together, these results show that functional human CD4+ and CD8+ eTregs can be generated from total human T cells by coexpressing FOXP3 and full-length Helios.
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