ArticleThe Journal of clinical investigation2011
Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Th17 cell pathogenicity in autoimmune disease.Experimental & molecular medicine · 2025Review
- Addressing the Role of Conventional CD8αβ+ T Cells and CD4+ T Cells in Intestinal Immunopathology Using a Bone Marrow-Engrafted Model.Bio-protocol · 2024Article
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- TGF-β signaling in health and disease.Cell · 2023Review
- Intricacies of TGF-β signaling in Treg and Th17 cell biology.Cellular & molecular immunology · 2023Review
- Transforming Growth Factor Beta Promotes Inflammation and Tumorigenesis in Smad4-Deficient Intestinal Epithelium in a YAP-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- SMAD4, activated by the TCR-triggered MEK/ERK signaling pathway, critically regulates CD8Science advances · 2022Article
- SMAD4 TGF-β-independent function preconditions naive CD8+ T cells to prevent severe chronic intestinal inflammation.The Journal of clinical investigation · 2022Article
- Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases.Cancer letters · 2022Article
- Overcoming TGFβ-mediated immune evasion in cancer.Nature reviews. Cancer · 2022Review
- The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis.Frontiers in immunology · 2022Review
- Transforming Growth Factor-β: An Agent of Change in the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Age-of-onset information helps identify 76 genetic variants associated with allergic disease.PLoS genetics · 2020Article
- BMP Signaling in Development, Stem Cells, and Diseases of the Gastrointestinal Tract.Annual review of physiology · 2020Review
- Immune battle at the premalignant stage of colorectal cancer: focus on immune cell compositions, functions and cytokine products.American journal of cancer research · 2020Review
- Review
- A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Review
- SMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium.Cancer research · 2018Article
- TGF-β-mediated enhancement of TScience signaling · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
While there is evidence that specific T cell populations can promote the growth of established tumors, instances where T cell activity causes neoplasms to arise de novo are infrequent. Here, we employed two conditional mutagenesis systems to delete the TGF-β signaling pathway component Smad4 in T cells and observed the spontaneous development of massive polyps within the gastroduodenal regions of mice. The epithelial lesions contained increased levels of transcripts encoding IL-11, IL-6, TGF-β, IL-1β, and TNF-α, and lamina propria cells isolated from lesions contained abundant IL-17A+CD4+ T cells. Furthermore, we found that Smad4 deficiency attenuated TGF-β-mediated in vitro polarization of FoxP3+CD4+ T cells, but not IL-17A+CD4+ T cells, suggesting that the epithelial lesions may have arisen as a consequence of unchecked Th17 cell activity. Proinflammatory cytokine production likely accounted for the raised levels of IL-11, a cytokine known to promote gastric epithelial cell survival and hyperplasia. Consistent with IL-11 having a pathogenic role in this model, we found evidence of Stat3 activation in the gastric polyps. Thus, our data indicate that a chronic increase in gut Th17 cell activity can be associated with the development of premalignant lesions of the gastroduodenal region.
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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.