ArticleJournal of immunology (Baltimore, Md. : 1950)2014
STAT3, STAT4, NFATc1, and CTCF regulate PD-1 through multiple novel regulatory regions in murine T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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Who cites it
109 citing papers in PubMed, 166 citations in OpenAlex.
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Review
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Prolonged TNF-α stimulation induces a PD-1-associated exhaustion-like phenotype in mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- Transcriptional dynamics of CD8Molecular cancer · 2025Article
- Review
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- The Regulatory Role of CTCF in IL6 Gene Transcription Assessed in Breast Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A Phase IB Trial of Selinexor in Combination With Immune Checkpoint Blockade in Patients With Advanced Renal Cell Carcinoma.Cancer medicine · 2025Article
- Effect of adipocytes on the function and activity of T cells in tumor microenvironment.Frontiers in immunology · 2025Review
- Rheumatoid arthritis associated cytokines and therapeutics modulate immune checkpoint receptor expression on T cells.Frontiers in immunology · 2025Article
- NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies.Therapeutic advances in medical oncology · 2025Article
- PD1-Targeted Transgene Delivery to Treg Cells.Viruses · 2024Article
- The Potential of PD-1 and PD-L1 as Prognostic and Predictive Biomarkers in Colorectal Adenocarcinoma Based on TILs Grading.Current oncology (Toronto, Ont.) · 2024Article
- Type I IFN Induces TCR-dependent and -independent Antimicrobial Responses in γδ Intraepithelial Lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Metformin Suppresses Both PD-L1 Expression in Cancer Cells and Cancer-Induced PD-1 Expression in Immune Cells to Promote Antitumor Immunity.Annals of laboratory medicine · 2024Article
- Spore Oil enhances the effect of cyclophosphamide inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Type I Interferon Activates PD-1 Expression through Activation of the STAT1-IRF2 Pathway in Myeloid Cells.Cells · 2024Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Programmed death-1 (PD-1) is a crucial negative regulator of CD8 T cell development and function, yet the mechanisms that control its expression are not fully understood. Through a nonbiased DNase I hypersensitivity assay, four novel regulatory regions within the Pdcd1 locus were identified. Two of these elements flanked the locus, bound the transcriptional insulator protein CCCTC-binding factor, and interacted with each other, creating a potential regulatory compartmentalization of the locus. In response to T cell activation signaling, NFATc1 bound to two of the novel regions that function as independent regulatory elements. STAT binding sites were identified in these elements as well. In splenic CD8 T cells, TCR-induced PD-1 expression was augmented by IL-6 and IL-12, inducers of STAT3 and STAT4 activity, respectively. IL-6 or IL-12 on its own did not induce PD-1. Importantly, STAT3/4 and distinct chromatin modifications were associated with the novel regulatory regions following cytokine stimulation. The NFATc1/STAT regulatory regions were found to interact with the promoter region of the Pdcd1 gene, providing a mechanism for their action. Together these data add multiple novel distal regulatory regions and pathways to the control of PD-1 expression and provide a molecular mechanism by which proinflammatory cytokines, such as IL-6 or IL-12, can augment PD-1 expression.
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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.