ArticleNature communications2021
EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Multiomic analysis identifies T cell subsets and mechanisms of epithelial interaction in idiopathic pulmonary fibrosis.JCI insight · 2026Article
- Red blood cell-derived extracellular vesicles enable cisplatin and cetuximab combined therapy against triple-negative breast cancer.Journal of nanobiotechnology · 2026Article
- Article
- Cellular metabolism in Th9, Th17, and Treg cell differentiation.International immunology · 2025Review
- Integrative transcriptomic profiling and machine learning reveal hypoxia-associated molecular signatures for precision diagnosis in thyroid eye disease.Human genomics · 2025Article
- Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis.NPJ biofilms and microbiomes · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Metabolic regulation of Th9 cell differentiation: insights for IL-9-driven diseases.Frontiers in immunology · 2025Review
- Regulatory mechanisms of Th9 cell differentiation.Frontiers in immunology · 2025Review
- Targeting Th9 cells in autoimmune diseases: a narrative review.Frontiers in immunology · 2025Review
- Platelets as a potential new immune coordinator in T cell-mediated aplastic anemia.Frontiers in oncology · 2025Review
- Berbamine prevents SARS-CoV-2 entry and transmission.iScience · 2024Article
- Natural lung-tropic TJournal for immunotherapy of cancer · 2024Article
- Intratumoral CXCL13Journal for immunotherapy of cancer · 2024Article
- Th9 Cytokines Inhibit Proliferation, Promote Apoptosis, and Immune Escape in Thyroid Carcinoma Cells.Applied biochemistry and biotechnology · 2024Article
- Locus of (IL-9) control: IL9 epigenetic regulation in cellular function and human disease.Experimental & molecular medicine · 2024Review
- Metabolic waypoints during T cell differentiation.Nature immunology · 2024Review
- Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy.Frontiers in immunology · 2024Review
- CoviWall, a whole-virion-inactivated B.1.617.2 vaccine candidate, induces potent humoral and Th1 cell response in mice and protects against B.1.617.2 strain challenge in Syrian hamsters.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Interleukin 9 (IL-9)-producing helper T (Th9) cells are essential for inducing anti-tumor immunity and inflammation in allergic and autoimmune diseases. Although transcription factors that are essential for Th9 cell differentiation have been identified, other signaling pathways that are required for their generation and functions are yet to be explored. Here, we identify that Epidermal Growth Factor Receptor (EGFR) is essential for IL-9 induction in helper T (Th) cells. Moreover, amphiregulin (Areg), an EGFR ligand, is critical for the amplification of Th9 cells induced by TGF-β1 and IL-4. Furthermore, our data show that Areg-EGFR signaling induces HIF1α, which binds and transactivates IL-9 and NOS2 promoters in Th9 cells. Loss of EGFR or HIF1α abrogates Th9 cell differentiation and suppresses their anti-tumor functions. Moreover, in line with its reliance on HIF1α expression, metabolomics profiling of Th9 cells revealed that Succinate, a TCA cycle metabolite, promotes Th9 cell differentiation and Th9 cell-mediated tumor regression.
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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.