ArticleScience signaling2016
The adhesion molecule PECAM-1 enhances the TGF-β-mediated inhibition of T cell function.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains a homeostatic Th17 cell state.Immunity · 2026Article
- Proteomic profiling of single extracellular vesicles reveals association of CD31Frontiers in immunology · 2026Article
- ScRNA profiling of peripheral blood in kidney transplant recipients across rejection responses and treatments.Scientific data · 2025Article
- The role of platelets in tumor immune evasion and metastasis: mechanisms and therapeutic implications.Cancer cell international · 2025Review
- Molecular characterization of suburothelial fibrosis in murine acute recurrent bladder inflammation.Scientific reports · 2025Article
- Single-cell transcriptomics reveals pathogen interactions and T cell reprogramming in HIV andFrontiers in immunology · 2025Article
- A human stem cell-derived model reveals pathologic extracellular matrix remodeling in diabetic podocyte injury.Matrix biology plus · 2024Article
- The different paradigms of NK cell death in patients with severe trauma.Cell death & disease · 2024Article
- Single-cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis.Thoracic cancer · 2024Article
- Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1β/CXCR2 Axis in Generation of Metastasis-specific Neutrophils.Cancer research communications · 2024Article
- Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.Kidney & blood pressure research · 2024Article
- CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- The diverse effects of transforming growth factor-β and SMAD signaling pathways during the CTL response.Frontiers in immunology · 2023Review
- Generation of PECAM-1 (CD31) conditional knockout mice.Genesis (New York, N.Y. : 2000) · 2020Article
- Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production.Journal of leukocyte biology · 2019Article
- Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8Journal of leukocyte biology · 2018Article
- Gene Modification of Transforming Growth Factor β (TGF-β) and Interleukin 10 (IL-10) in Suppressing Mt Sonicate Induced Osteoclast Formation and Bone Absorption.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer.Frontiers in cell and developmental biology · 2016Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits the proinflammatory functions of T cells, and it is a major factor in abrogating T cell activity against tumors. Canonical TGF-β signaling results in the activation of Smad proteins, which are transcription factors that regulate target gene expression. We found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) TGF-β signaling in T cells. Subcutaneously injected tumor cells that are dependent on TGF-β-mediated suppression of immunity for growth grew more slowly in PECAM-1(-/-) mice than in their wild-type counterparts. T cells isolated from PECAM-1(-/-) mice demonstrated relative insensitivity to the TGF-β-dependent inhibition of interferon-γ (IFN-γ) production, granzyme B synthesis, and cellular proliferation. Similarly, human T cells lacking PECAM-1 demonstrated decreased sensitivity to TGF-β in a manner that was partially restored by reexpression of PECAM-1. Co-incubation of T cells with TGF-β and a T cell-activating antibody resulted in PECAM-1 phosphorylation on an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the recruitment of the inhibitory Src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP-2). Such conditions also induced the colocalization of PECAM-1 with the TGF-β receptor complex as identified by coimmunoprecipitation, confocal microscopy, and proximity ligation assays. These studies indicate a role for PECAM-1 in enhancing the inhibitory functions of TGF-β in T cells and suggest that therapeutic targeting of the PECAM-1-TGF-β inhibitory axis represents a means to overcome TGF-β-dependent immunosuppression within the tumor microenvironment.
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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.