ArticleNature medicine2013
CD28 and ITK signals regulate autoreactive T cell trafficking.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 40 citations in OpenAlex.
- Discovery of an ITK and TRK kinase inhibitor for the potential topical treatment of atopic dermatitis.Nature communications · 2026Article
- Balancing immune activation with Itk.Trends in pharmacological sciences · 2024Article
- CD8ImmunoHorizons · 2020Article
- ITK inhibition promotes long-term survival of cardiac allografts by regulating T cell PLCγ phosphorylation.American journal of translational research · 2020Article
- Prognostic significance of peripheral CD8+CD28+ and CD8+CD28- T cells in advanced non-small cell lung cancer patients treated with chemo(radio)therapy.Journal of translational medicine · 2019Article
- Dichotomous roles of co-stimulatory molecules in diabetes mellitus.Oncotarget · 2018Review
- CTLA-4: a moving target in immunotherapy.Blood · 2018Review
- T Cell Receptor-Major Histocompatibility Complex Interaction Strength Defines Trafficking and CD103Frontiers in immunology · 2018Article
- The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease.Frontiers in immunology · 2018Review
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- Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Quantitative analysis of B-lymphocyte migration directed by CXCL13.Integrative biology : quantitative biosciences from nano to macro · 2016Article
- Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.American journal of respiratory cell and molecular biology · 2016Article
- A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Confusing signals: recent progress in CTLA-4 biology.Trends in immunology · 2015Review
- Itk signals promote neuroinflammation by regulating CD4+ T-cell activation and trafficking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes.Frontiers in immunology · 2015Review
- Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.PloS one · 2015Article
- Immunodeficiency and immune dysregulation associated with proximal defects of T cell receptor signaling.Current opinion in immunology · 2014Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of self-reactive T cells and their trafficking to target tissues leads to autoimmune organ destruction. Mice lacking the co-inhibitory receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) develop fatal autoimmunity characterized by lymphocytic infiltration into nonlymphoid tissues. Here, we demonstrate that the CD28 co-stimulatory pathway regulates the trafficking of self-reactive Ctla4(-/-) T cells to tissues. Concurrent ablation of the CD28-activated Tec family kinase ITK does not block spontaneous T cell activation but instead causes self-reactive Ctla4(-/-) T cells to accumulate in secondary lymphoid organs. Despite excessive spontaneous T cell activation and proliferation in lymphoid organs, Itk(-/-); Ctla4(-/-) mice are otherwise healthy, mount antiviral immune responses and exhibit a long lifespan. We propose that ITK specifically licenses autoreactive T cells to enter tissues to mount destructive immune responses. Notably, ITK inhibitors mimic the null mutant phenotype and also prevent pancreatic islet infiltration by diabetogenic T cells in mouse models of type 1 diabetes, highlighting their potential utility for the treatment of human autoimmune disorders.
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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.