ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Mitochondrial reactive oxygen species regulate acetyl-CoA flux between cytokine production and fatty acid synthesis in effector T cells.Cell reports · 2025Article
- p53: A player in the tumor microenvironment.Oncology research · 2025Review
- Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.Science immunology · 2024Article
- p53 at the crossroads of tumor immunity.Nature cancer · 2024Review
- Suppression of P53 Pathway is an Important Factor Inducing Acute Graft-versus-Host Disease Through T Cell Activation Based on Bioinformatics Analysis.Journal of inflammation research · 2024Article
- Forecasting of potential anti-inflammatory targets of some immunomodulatory plants and their constituents using in vitro, molecular docking and network pharmacology-based analysis.Scientific reports · 2023Article
- Deficiency of p53 Causes the Inadequate Expression of miR-1246 in B Cells of Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- Review
- Dysregulated TP53 Among PTSD Patients Leads to Downregulation of miRNA let-7a and Promotes an Inflammatory Th17 Phenotype.Frontiers in immunology · 2021Article
- A Different Facet of p53 Function: Regulation of Immunity and Inflammation During Tumor Development.Frontiers in cell and developmental biology · 2021Review
- The Role of the IL-23/IL-17 Axis in Disease Initiation in Spondyloarthritis: Lessons Learned From Animal Models.Frontiers in immunology · 2021Review
- Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses.Cell reports · 2020Article
- Downregulation of p53 by Insufficient CTCF in CD4Frontiers in immunology · 2020Article
- Article
- Review
- Loss ofFrontiers in immunology · 2018Article
- Article
- miR-34a and miR-125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus.Experimental and therapeutic medicine · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Emerging evidence suggests that the tumor suppressor p53 is also a crucial regulator for many physiological processes. Previous observations indicate that p53 suppresses inflammation by inhibiting inflammatory antigen-presenting cells. To investigate the potential role of p53 in autoimmune effector T cells, we generated p53(null)CD45.1 mice by crossing p53(null)CD45.2 and CD45.1 mice. We demonstrate that p53(null)CD45.1 mice spontaneously developed autoimmunity, with a significant increase in IL-17-producing Th17 effectors in their lymph nodes (4.7 ± 1.0%) compared to the age-matched counterparts (1.9 ± 0.8% for p53(null)CD45.2, 1.1 ± 0.2% for CD45.1, and 0.5 ± 0.1% for CD45.2 mice). Likewise, p53(null)CD45.1 mice possess highly elevated serum levels of inflammatory cytokines IL-17 and IL-6. This enhanced Th17 response results largely from an increased sensitivity of p53(null)CD45.1 T cells to IL-6-induced STAT3 phosphorylation. Administration of STAT3 inhibitor S31-201 (IC50 of 38.0 ± 7.2 μM for IL-6-induced STAT3 phosphorylation), but not PBS control, to p53(null)CD45.1 mice suppressed Th17 effectors and alleviated autoimmune pathology. This is the first report revealing that p53 activity in T cells suppresses autoimmunity by controlling Th17 effectors. This study suggests that p53 serves as a guardian of immunological functions and that the p53-STAT3-Th17 axis might be a therapeutic target for autoimmunity.
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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.