ArticleThe Journal of experimental medicine2009
Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 108 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
108 citing papers in PubMed, 219 citations in OpenAlex.
- Trial
- Platelets as non-canonical immune regulatory nodes: orchestrating T cell dysfunction and immunotherapy resistance in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Mesenchymal stem cells alleviate experimental cerebral malaria disease severity by inducing RoRγtCell death discovery · 2026Article
- CD4Frontiers in immunology · 2026Review
- Th17 cell pathogenicity in autoimmune disease.Experimental & molecular medicine · 2025Review
- Transforming growth factors β and their signaling pathway in renal cell carcinoma and peritumoral space-transcriptome analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Th17 cytokines and factors modulating their activity in patients with pernicious anemia.Immunologic research · 2023Article
- Tehranolid and Artemisinin Effects on Ameliorating Experimental Autoimmune Encephalomyelitis by Modulating Inflammation and Remyelination.Molecular neurobiology · 2023Article
- Intricacies of TGF-β signaling in Treg and Th17 cell biology.Cellular & molecular immunology · 2023Review
- The transcriptional regulator Sin3A balances IL-17A and Foxp3 expression in primary CD4 T cells.EMBO reports · 2023Article
- Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion.Pharmaceutical biology · 2022Article
- Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages.iScience · 2022Article
- Migration and homeostasis of regulatory T cells in rheumatoid arthritis.Frontiers in immunology · 2022Review
- New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.Frontiers in pediatrics · 2022Review
- miR-99a regulates CD4Molecular therapy. Nucleic acids · 2021Article
- Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation.The Journal of experimental medicine · 2021Article
- Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity.Journal of neuroimmunology · 2021Article
- TGF-β Signaling: From Tissue Fibrosis to Tumor Microenvironment.International journal of molecular sciences · 2021Review
- LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis.Molecular medicine (Cambridge, Mass.) · 2021Article
- Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus.Cellular & molecular immunology · 2021Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Interleukin (IL)-17-producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) beta, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-beta exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-beta does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-beta had no effect on the expression of retinoic acid receptor-related orphan nuclear receptor gammat, a Th17-specific transcription factor. Interestingly, in Stat-6(-/-)T-bet(-/-) mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-beta had no effect, suggesting that TGF-beta is dispensable for Th17 cell development. Consequently, BALB/c Stat-6(-/-)T-bet(-/-) mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti-IL-17 antibodies but not by anti-TGF-beta antibodies. Collectively, these data provide evidence that TGF-beta is not directly required for the molecular orchestration of Th17 cell differentiation.
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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.