ArticleImmunology and cell biology2015
Activation of TGF-β-induced non-Smad signaling pathways during Th17 differentiation.
Article in Immunology and cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
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- Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis.International journal of molecular sciences · 2023Article
- Morin, the PPARγ agonist, inhibits Th17 differentiation by limiting fatty acid synthesis in collagen-induced arthritis.Cell biology and toxicology · 2023Article
- Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy.Molecular cancer · 2023Review
- Epigenetic modulations of immune cells: from normal development to tumor progression.International journal of biological sciences · 2023Review
- Cell division control protein 42 correlates with lower disease risk and its elevation predicts better treatment response, and inhibits T-helper 17 cell differentiation in rheumatoid arthritis.Inflammopharmacology · 2022Article
- Active fractions of golden-flowered tea (Frontiers in nutrition · 2022Article
- Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis.Antioxidants (Basel, Switzerland) · 2021Review
- Epigenetic Reprogramming of CD4Frontiers in immunology · 2021Review
- Smad7 in intestinal CD4Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Review
- Transforming growth factor-β signaling in systemic sclerosis.Journal of biomedical research · 2018Article
- Akt2 Regulates the Differentiation and Function of NKT17 Cells via FoxO-1-ICOS Axis.Frontiers in immunology · 2018Article
- Simulation of Stimulation: Cytokine Dosage and Cell Cycle Crosstalk Driving Timing-Dependent T Cell Differentiation.Frontiers in physiology · 2018Article
- TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut.Nature communications · 2017Article
- Naturally occurring compounds acting as potent anti-metastatic agents and their suppressing effects on Hedgehog and WNT/β-catenin signalling pathways.Cell proliferation · 2017Review
- PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.Scientific reports · 2017Article
- Smad4 in T cells plays a protective role in the development of autoimmune Sjögren's syndrome in the nonobese diabetic mouse.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although transforming growth factor-β (TGF-β) has been shown to positively regulate the development of murine T helper type 17 (Th17) cells, which of the intracellular signaling pathways are involved is controversial. We examined Smad-dependent and -independent signaling molecules downstream of the TGF-β receptor (TGFβR) involved in Th17 differentiation of naive murine CD4(+)CD62L(+) T cells. During Th17 differentiation of wild-type T cells, Smad2/3 was phosphorylated, indicating activation of the canonical Smad pathway. T cells lacking TGFβRII did not differentiate into Th17, whereas T cells treated with a TGFβRI kinase inhibitor (SB-431542) or overexpression of inhibitory Smad7 retained a low amount of Th17 polarization despite absent Smad2/3 phosphorylation. Using protein antibody arrays we found an increase of expression and phosphorylation of the following Smad-independent signaling molecules in Th17-polarized wild-type T cells: AKT1(Tyr474), AKT2 (Ser474), ERK1-p44/42 MAPK(Tyr204), mTOR(Thr2446), p38 MAPK(Thr180), Rac1/cdc42(Ser71), SAPK/JNK(Tyr185) and SP1(Thr739). Pharmacological inhibition of AKT/mammalian target of rapamycin (mTOR) signaling with rapamycin or LY294002 decreased Th17 differentiation of wild-type T cells, and completely abolished interleukin-17 production in T cells with overexpression of Smad7. Rapamycin and LY294002 also decreased induced regulatory T cell differentiation, but only had minor additive effects to Smad7 overexpression. Finally, inhibitors of mitogen-activated protein kinase (MAPK) blocked in vitro polarization of Th17 cells. Our data show that Smad-dependent and -independent intracellular pathways contribute to murine Th17 differentiation.
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