ArticlePloS one2012
CD28 costimulation regulates genome-wide effects on alternative splicing.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
24 citing papers in PubMed, 50 citations in OpenAlex.
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Regulation of CD45 isoforms during human effector and memory CD8 T cell differentiation: Implications for T cell nomenclature.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer.Cell death & disease · 2025Review
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Article
- CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity.Cellular & molecular immunology · 2024Article
- Extensive Alternative Splicing Patterns in Systemic Lupus Erythematosus Highlight Sexual Differences.Cells · 2023Article
- Article
- Article
- Co-Stimulatory Receptor Signaling in CAR-T Cells.Biomolecules · 2022Review
- Optimal CD8Nature communications · 2022Article
- Alternative Splicing in Cancer and Immune Cells.Cancers · 2022Review
- Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation.Molecular and cellular biology · 2019Article
- TLR4 signaling improves PD-1 blockade therapy during chronic viral infection.PLoS pathogens · 2019Article
- Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.Wiley interdisciplinary reviews. RNA · 2018Review
- Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.Frontiers in immunology · 2018Review
- Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8Frontiers in immunology · 2018Article
- Splicing in immune cells-mechanistic insights and emerging topics.International immunology · 2017Review
- Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4Frontiers in immunology · 2017Article
- CD28 Costimulation: From Mechanism to Therapy.Immunity · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
CD28 is the major costimulatory receptor required for activation of naïve T cells, yet CD28 costimulation affects the expression level of surprisingly few genes over those altered by TCR stimulation alone. Alternate splicing of genes adds diversity to the proteome and contributes to tissue-specific regulation of genes. Here we demonstrate that CD28 costimulation leads to major changes in alternative splicing during activation of naïve T cells, beyond the effects of TCR alone. CD28 costimulation affected many more genes through modulation of alternate splicing than by modulation of transcription. Different families of biological processes are over-represented among genes alternatively spliced in response to CD28 costimulation compared to those genes whose transcription is altered, suggesting that alternative splicing regulates distinct biological effects. Moreover, genes dependent upon hnRNPLL, a global regulator of splicing in activated T cells, were enriched in T cells activated through TCR plus CD28 as compared to TCR alone. We show that hnRNPLL expression is dependent on CD28 signaling, providing a mechanism by which CD28 can regulate splicing in T cells and insight into how hnRNPLL can influence signal-induced alternative splicing in T cells. The effects of CD28 on alternative splicing provide a newly appreciated means by which CD28 can regulate T cell responses.
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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.