ArticleJournal of Crohn's & colitis2022
PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells.
Article in Journal of Crohn's & colitis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Th9 cells at the intersection of IBD and colorectal cancer: a context-dependent factor in carcinogenesis.Inflammation and regeneration · 2026Review
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Stearoyl-CoA desaturase-1 controls the differentiation and antitumoral function of Th9 lymphocytes.Journal for immunotherapy of cancer · 2026Article
- ARID1A deficiency promotes malignant proliferation of hepatocellular carcinoma by activating HDAC7/ENO1 signaling pathway.Hepatology communications · 2025Article
- Application of single-cell sequencing in the study of immune cell infiltration in inflammatory bowel disease and colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer.Frontiers in immunology · 2025Article
- Targeting Th9 cells in autoimmune diseases: a narrative review.Frontiers in immunology · 2025Review
- PU.1 upregulation is linked to improved prognosis in non-small cell lung cancer.Frontiers in immunology · 2025Article
- Multi-omics approaches reveal the mechanisms underlying the interaction between cyst fluid ofFrontiers in immunology · 2025Article
- Tumor-Infiltrating Immune Cells in Colorectal Cancer.Neoplasia (New York, N.Y.) · 2025Review
- The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.Journal of translational medicine · 2024Review
- Th9 and Th17 Cells in Human Ulcerative Colitis-Associated Dysplastic Lesions.Clinical Medicine Insights. Oncology · 2024Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- The Dichotomy of Interleukin-9 Function in the Tumor Microenvironment.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
- Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis.Frontiers in immunology · 2023Article
- How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsColorectal cancer [CRC] is one of the most frequent malignancies, but the molecular mechanisms driving cancer growth are incompletely understood. We characterised the roles of the cytokine IL-9 and Th9 cells in regulating CRC development.
methodsCRC patient samples and samples from AOM/DSS treated mice were analysed for expression of IL-9, CD3, and PU.1 by FACS analysis and immunohistochemistry. IL-9 citrine reporter mice, IL-9 knockout mice, and PU.1 and GATA3 CD4-Cre conditional knockout mice were studied in the AOM/DSS model. DNA minicircles or hyper-IL-6 were used for overexpression of cytokines in vivo. Effects of IL-6 and IL-9 were determined in organoid and T cell cultures. Claudin2/3 expression was studied by western blotting and bacterial translocation by FISH.
resultsWe uncovered a significant expansion of IL-9- and PU.1-expressing mucosal Th9 cells in CRC patients, with particularly high levels in patients with colitis-associated neoplasias. PU.1+ Th9 cells accumulated in experimental colorectal neoplasias. Deficiency of IL-9 or inactivation of PU.1 in T cells led to impaired tumour growth in vivo, suggesting a protumoral role of Th9 cells. In contrast, GATA3 inactivation did not affect Th9-mediated tumour growth. Mechanistically, IL-9 controls claudin2/3 expression and T cell-derived IL-6 production in colorectal tumours. IL-6 abrogated the anti-proliferative effects of IL-9 in epithelial organoids in vivo. IL-9-producing Th9 cells expand in CRC and control IL-6 production by T cells.
conclusionsIL-9 is a crucial regulator of tumour growth in colitis-associated neoplasias and emerges as potential target for therapy.
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