ArticlePloS one2011
The dynamic processing of CD46 intracellular domains provides a molecular rheostat for T cell activation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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.
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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
45 citing papers in PubMed, 68 citations in OpenAlex.
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- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Low CD46 expression on activated CD4Frontiers in allergy · 2024Article
- Complement, complosome, and complotype: A perspective.European journal of immunology · 2023Review
- Complosome - the intracellular complement system.Nature reviews. Nephrology · 2023Review
- The Complement System in Kidney Transplantation.Cells · 2023Review
- Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.Pediatric research · 2022Article
- CD46 Isoforms Influence the Mode of Entry by Human Herpesvirus 6A/B in T Cells.Journal of virology · 2022Article
- Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application.Frontiers in immunology · 2022Review
- CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer.Molecular therapy. Nucleic acids · 2021Article
- The RNA binding protein SRSF1 is a master switch of gene expression and regulation in the immune system.Cytokine & growth factor reviews · 2021Review
- Renal diseases and the role of complement: Linking complement to immune effector pathways and therapeutics.Advances in immunology · 2021Review
- A robust and interpretable end-to-end deep learning model for cytometry data.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Complement and human T cell metabolism: Location, location, location.Immunological reviews · 2020Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAdequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated. METHODOLOGY/PRINCIPAL
findingsHere, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually. CONCLUSIONS/SIGNIFICANCE: We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails.
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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.