ArticleProceedings of the National Academy of Sciences of the United States of America2016
Peripheral tolerance can be modified by altering KLF2-regulated Treg migration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-Analysis of Genome-Wide Association and Gene Expression Studies Implicates Donor T Cell Function and Cytokine Pathways in Acute GvHD.Frontiers in immunology · 2020Pooled it
- Review
- CNS1-dependent regulatory T cells shape recovery from acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Maternal Krüppel-like factor 2 (KLF2)+ CD4 T cells promote fertility and fetal tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regulatory T cells and peripheral immune tolerance: key mechanisms and therapeutic strategies for cardiovascular diseases.Frontiers in immunology · 2026Review
- The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis.Frontiers in immunology · 2025Review
- Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Kruppel-like factor 2+ CD4 T cells avert microbiota-induced intestinal inflammation.Cell reports · 2023Article
- Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- Single-Cell RNA Sequencing Reveals Unique Alterations in the Immune Panorama and Treg Subpopulations in Mice during the Late Stages of Echinococcus granulosus Infection.Infection and immunity · 2023Article
- Krüppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses.Mucosal immunology · 2022Article
- PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome.Frontiers in immunology · 2022Article
- Heterozygous premature termination in zinc-finger domain of Krüppel-like factor 2 gene associates with dysregulated immunity.Frontiers in immunology · 2022Article
- Krüppel-like Factor 2 (KLF2) in Immune Cell Migration.Vaccines · 2021Review
- TCF-1 controls TNature immunology · 2021Article
- Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool.Cellular & molecular immunology · 2021Article
- miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway.Cell cycle (Georgetown, Tex.) · 2020Article
- Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein.Life science alliance · 2020Article
- Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function under the Regulation of KLF2.BioMed research international · 2020Article
- High concentrations of atorvastatin reduce in-vitro function of conventional T and regulatory T cells.Clinical and experimental immunology · 2019Article
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Authors and funding
9 authors.
Funding
Abstract
Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolerance under physiologically relevant conditions. We now report that transcription factor Kruppel-like factor 2 (KLF2) controls naive Treg migration patterns via regulation of homeostatic and inflammatory homing receptors, and that in its absence KLF2-deficient Tregs are unable to migrate efficiently to secondary lymphoid organs (SLOs). Diminished Treg trafficking to SLOs is sufficient to initiate autoimmunity, indicating that SLOs are a primary site for maintaining peripheral tolerance under homeostatic conditions. Disease severity correlates with impaired Treg recruitment to SLOs and, conversely, promotion of Tregs into these tissues can ameliorate autoimmunity. Moreover, stabilizing KLF2 expression within the Treg compartment enhances peripheral tolerance by diverting these suppressive cells from tertiary tissues into SLOs. Taken together, these results demonstrate that peripheral tolerance is enhanced or diminished through modulation of Treg trafficking to SLOs, a process that can be controlled by adjusting KLF2 protein levels.
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