ArticleThe Journal of biological chemistry2009
Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 93 citations in OpenAlex.
- Review
- Persistent CD4Cellular immunology · 2026Article
- The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion.Animal cells and systems · 2026Review
- CaCell death discovery · 2024Article
- Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study.Journal of thoracic disease · 2024Article
- Klf9 plays a critical role in GR -dependent metabolic adaptations in cardiomyocytes.Cellular signalling · 2023Article
- Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma.Cancers · 2023Review
- Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model.iScience · 2023Article
- CD83 Regulates the Immune Responses in Inflammatory Disorders.International journal of molecular sciences · 2023Review
- Zinc in Human Health and Infectious Diseases.Biomolecules · 2022Review
- Perivascular Fibrosis Is Mediated by a KLF10-IL-9 Signaling Axis in CD4+ T Cells.Circulation research · 2022Article
- Somatic FOXC1 insertion mutation remodels the immune microenvironment and promotes the progression of childhood acute lymphoblastic leukemia.Cell death & disease · 2022Article
- Deciphering the Role ofJournal of biomedical science and engineering · 2022Article
- Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation.International journal of molecular sciences · 2022Review
- Crucial role of T cells in NAFLD-related disease: A review and prospect.Frontiers in endocrinology · 2022Review
- Fine-tuning of regulatory T cells is indispensable for the metabolic steatosis-related hepatocellular carcinoma: A review.Frontiers in cell and developmental biology · 2022Review
- PD-L1Nature communications · 2021Article
- The basal transcriptional activity of the murine Klf10 gene is regulated by the transcriptional factor JunB.Genes & genomics · 2021Article
- KLF10 Deficiency in CD4Cell reports · 2020Article
- A macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus.Nature communications · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance and immune suppression, although the mechanisms controlling T reg development and suppressor function remain incompletely understood. Herein, we provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an important regulator of T regulatory cell suppressor function and CD4(+)CD25(-) T cell activation through distinct mechanisms involving transforming growth factor (TGF)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both TGF-beta1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1 marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10(-/-) CD4(+)CD25(-) T cells have enhanced differentiation along both Th1 and Th2 pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore, KLF10(-/-) CD4(+)CD25(-) T cell effectors cannot be appropriately suppressed by wild-type T regs. Surprisingly, KLF10(-/-) T reg cells have reduced suppressor function, independent of Foxp3 expression, with decreased expression and elaboration of TGF-beta1, an effect completely rescued by exogenous treatment with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1, KLF10 can transactivate both TGF-beta1 and Foxp3 promoters, implicating KLF10 in a positive feedback loop that may promote cell-intrinsic control of T cell activation. Finally, KLF10(-/-) CD4(+)CD25(-) T cells promoted atherosclerosis by approximately 2-fold in ApoE(-/-)/scid/scid mice with increased leukocyte accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-beta1 in both CD4(+)CD25(-) T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice.
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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.