ArticleThe Journal of biological chemistry2012
Leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction induces a novel genetic signature resulting in T-cells refractory to transforming growth factor-β signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Review
- The Role of LFA-1 for the Differentiation and Function of Regulatory T Cells-Lessons Learned from Different Transgenic Mouse Models.International journal of molecular sciences · 2023Review
- Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.Nature immunology · 2021Article
- LFA-1 in T cell priming, differentiation, and effector functions.Trends in immunology · 2021Review
- Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity.British journal of pharmacology · 2021Review
- Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets.Cell reports · 2021Article
- Cysteine Cathepsins in Tumor-Associated Immune Cells.Frontiers in immunology · 2019Review
- Beta2-Integrins and Interacting Proteins in Leukocyte Trafficking, Immune Suppression, and Immunodeficiency Disease.Frontiers in immunology · 2019Review
- CG-NAP/Kinase Interactions Fine-Tune T Cell Functions.Frontiers in immunology · 2019Review
- Interleukin-1Stem cells international · 2019Article
- Review
- Centrosome- and Golgi-Localized Protein Kinase N-Associated Protein Serves As a Docking Platform for Protein Kinase A Signaling and Microtubule Nucleation in Migrating T-Cells.Frontiers in immunology · 2018Article
- Role of LFA-1 and ICAM-1 in Cancer.Cancers · 2017Review
- G-CSF inhibits LFA-1-mediated CD4Oncotarget · 2017Article
- CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer.Theranostics · 2017Article
- GapmeR cellular internalization by macropinocytosis induces sequence-specific gene silencing in human primary T-cells.Scientific reports · 2016Article
- A novel multi-parameter assay to dissect the pharmacological effects of different modes of integrin αLβ2 inhibition in whole blood.British journal of pharmacology · 2015Article
- Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3⁺ Treg cells.Journal of immunological methods · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunesuppressive cytokine TGF-β plays crucial regulatory roles in the induction and maintenance of immunologic tolerance and prevention of immunopathologies. However, it remains unclear how circulating T-cells can escape from the quiescent state maintained by TGF-β. Here, we report that the T-cell integrin leukocyte function-associated antigen-1 (LFA-1) interaction with its ligand intercellular adhesion molecule-1 (ICAM-1) induces a genetic signature associated with reduced TGF-β responsiveness via up-regulation of SKI, E3 ubiquitin-protein ligase SMURF2, and SMAD7 (mothers against decapentaplegic homolog 7) genes and proteins. We confirmed that the expression of these TGF-β inhibitory molecules was dependent on STAT3 and/or JNK activation. Increased expression of SMAD7 and SMURF2 in LFA-1/ICAM-1 cross-linked T-cells resulted in impaired TGF-β-mediated phosphorylation of SMAD2 and suppression of IL-2 secretion. Expression of SKI caused resistance to TGF-β-mediated suppression of IL-2, but SMAD2 phosphorylation was unaffected. Blocking LFA-1 by neutralizing antibody or specific knockdown of TGF-β inhibitory molecules by siRNA substantially restored LFA-1/ICAM-1-mediated alteration in TGF-β signaling. LFA-1/ICAM-1-stimulated human and mouse T-cells were refractory to TGF-β-mediated induction of FOXP3(+) (forkhead box P3) and RORγt(+) (retinoic acid-related orphan nuclear receptor γt) Th17 differentiation. These mechanistic data suggest an important role for LFA-1/ICAM-1 interactions in immunoregulation concurrent with lymphocyte migration that may have implications at the level of local inflammatory response and for anti-LFA-1-based therapies.
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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.