ArticleThe Journal of experimental medicine2016
The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- Trial
- Allogeneic hematopoietic cell transplantation is curative in CARMIL2 deficiency.Journal of human immunity · 2026Article
- Cell-type specific analyses in blood and gut identify cis-eQTL matching 140 IBD risk loci and entrectinib as repurposing candidate.Nature communications · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Gallic acid chemoprevention of oral carcinogenesis is associated with HSD11β2 upregulation and immune remodeling.Scientific reports · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Coordinated regulation of Capping Protein by CARMIL and V-1/myotrophin.The Journal of biological chemistry · 2026Review
- A CARMIL2 gain-of-function mutation suffices to trigger most CD28 costimulatory functions in vivo.The Journal of experimental medicine · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- A NovelJournal of fungi (Basel, Switzerland) · 2024Article
- Consequences of COVID-19 on Adipose Tissue Signatures.International journal of molecular sciences · 2024Article
- Novel CARMIL2 (RLTPR) Mutation Presenting with Hyper-IgE and Eosinophilia: A Case Report.Endocrine, metabolic & immune disorders drug targets · 2024Article
- TCR Pathway Mutations in Mature T Cell Lymphomas.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
- Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island.Biomedicines · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.The Journal of experimental medicine · 2023Article
- The role of the CBM complex in allergic inflammation and disease.The Journal of allergy and clinical immunology · 2022Review
- Dual regulation of the actin cytoskeleton by CARMIL-GAP.Journal of cell science · 2022Article
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
Abstract
The RLTPR cytosolic protein, also known as CARMIL2, is essential for CD28 co-stimulation in mice, but its importance in human T cells and mode of action remain elusive. Here, using affinity purification followed by mass spectrometry analysis, we showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-κB signaling pathway, and identified proteins not found before within the CD28 signaling pathway. We further demonstrated that RLTPR is essential for CD28 co-stimulation in human T cells and that its noncanonical pleckstrin-homology domain, leucine-rich repeat domain, and proline-rich region were mandatory for that task. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 co-stimulation in both mouse and human. Our findings suggest that the scaffolding role of RLTPR predominates during CD28 co-stimulation and underpins the similar function of RLTPR in human and mouse T cells. Along that line, the lack of functional RLTPR molecules impeded the differentiation toward Th1 and Th17 fates of both human and mouse CD4
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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.