ArticleImmunology2021
Regulation of CTLA-4 recycling by LRBA and Rab11.
Article in Immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- A homozygous CTLA-4 variant causes CTLA-4 deficiency with severe immune dysregulation.Journal of human immunity · 2026Article
- Early Prediction of Non-recovery in Drug-induced Liver Injury by Integrating Genetic Variants and Clinical Variables: An Interpretable Machine Learning Approach.Journal of clinical and translational hepatology · 2026Article
- LRBA regulates actin cytoskeleton dynamics through NMIIA during B cell immune responses.EMBO reports · 2026Article
- Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4): Between immune tolerance and genetic predisposition to Systemic Lupus Erythematosus (SLE).Journal of translational autoimmunity · 2026Review
- Review
- LRBA organizes distinct vesicular trafficking systems in distal nephron segments for water and sodium conservation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Cell death and immune escape in the tumor microenvironment: associated mechanisms, opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Gatekeepers of immunity: mechanisms and regulation of immune checkpoints and their role in immune-privileged sites.Molecular biology reports · 2025Review
- Targeting LRBA triggers CTLA4 degradation and antitumor immunity for cancer immunotherapy.Nature communications · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- LRBA deficiency impairs autophagy and contributes to enhanced antigen presentation and T-cell dysregulation.EMBO reports · 2025Article
- ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis.Nature communications · 2025Article
- Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.The Journal of cell biology · 2025Article
- CD28 and TCR differentially impact naïve and memory T cell responses.Discovery immunology · 2025Article
- An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.Cell reports · 2024Article
- An overview on the interaction between non-coding RNAs and CTLA-4 gene in human diseases.Medical oncology (Northwood, London, England) · 2024Review
- Article
- Lrba participates in the differentiation of IgA+ B lymphocytes through TGFβR signaling.Frontiers in immunology · 2024Article
- Rapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
CTLA-4 is an essential regulator of T-cell immune responses whose intracellular trafficking is a hallmark of its expression. Defects in CTLA-4 trafficking due to LRBA deficiency cause profound autoimmunity in humans. CTLA-4 rapidly internalizes via a clathrin-dependent pathway followed by poorly characterized recycling and degradation fates. Here, we explore the impact of manipulating Rab GTPases and LRBA on CTLA-4 expression to determine how these proteins affect CTLA-4 trafficking. We observe that CTLA-4 is distributed across several compartments marked by Rab5, Rab7 and Rab11 in both HeLa and Jurkat cells. Dominant negative (DN) inhibition of Rab5 resulted in increased surface CTLA-4 expression and reduced internalization and degradation. We also observed that constitutively active (CA) Rab11 increased, whereas DN Rab11 decreased CTLA-4 surface expression via an impact on CTLA-4 recycling, indicating CTLA-4 shares similarities with other recycling receptors such as EGFR. Additionally, we studied the impact of manipulating both LRBA and Rab11 on CTLA-4 trafficking. In Jurkat cells, LRBA deficiency was associated with markedly impaired CTLA-4 recycling and increased degradation that could not be corrected by expressing CA Rab11. Moreover LRBA deficiency reduced CTLA-4 colocalization with Rab11, suggesting that LRBA is upstream of Rab11. These results show that LRBA is required for effective CTLA-4 recycling by delivering CTLA-4 to Rab11 recycling compartments, and in its absence, CTLA-4 fails to recycle and undergoes degradation.
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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.