ArticleJournal of immunology (Baltimore, Md. : 1950)2009
ERK-dependent T cell receptor threshold calibration in rheumatoid arthritis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Molecular insights into phytochemicals exhibiting anti-arthritic activity: systematic review : John Di Battista.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Pooled it
- A druggable redox switch on SHP1 controls macrophage inflammation.Nature chemical biology · 2026Article
- A druggable redox switch on SHP1 controls macrophage inflammation.bioRxiv : the preprint server for biology · 2026Article
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T-Cell Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Analysis ofDiagnostics (Basel, Switzerland) · 2023Article
- Ras family signaling pathway in immunopathogenesis of inflammatory rheumatic diseases.Frontiers in immunology · 2023Review
- The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection.Nature communications · 2022Article
- Ceramide synthase 6 impacts T-cell allogeneic response and graft-versus-host disease through regulating N-RAS/ERK pathway.Leukemia · 2022Article
- Treating 'Septic' With Enhanced Antibiotics and 'Arthritis' by Mitigation of Excessive Inflammation.Frontiers in cellular and infection microbiology · 2022Article
- Hallmarks of the aging T-cell system.The FEBS journal · 2021Review
- Decreased Levels of STAT1 and Interferon-γ-Induced STAT1 Phosphorylation in Rheumatoid Arthritis CD4 and CD8 T Cells.ACR open rheumatology · 2021Article
- PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.PLoS biology · 2021Article
- Clinical Evidence-Guided Anti-rheumatoid Arthritis Study of Shuji Tablet in Adjuvant-Induced Arthritis Rats and Mechanism ExplorationFrontiers in pharmacology · 2021Article
- Small GTPase RAS in multiple sclerosis - exploring the role of RAS GTPase in the etiology of multiple sclerosis.Small GTPases · 2020Review
- Inhibition of Ras GTPases prevents Collagen-Induced Arthritis by Reducing the Generation of Pathogenic CD4ACR open rheumatology · 2020Article
- Granulomatosis with polyangiitis in a patient treated with dabrafenib and trametinib for BRAF V600E positive lung adenocarcinoma.BMC cancer · 2020Article
- Dendritic cells, T cells and their interaction in rheumatoid arthritis.Clinical and experimental immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Immune responses to citrullinated neoantigens and clinical efficacy of costimulation blockade indicate a general defect in maintaining T cell tolerance in rheumatoid arthritis (RA). To examine whether TCR threshold calibration contributes to disease pathogenesis, signaling in RA T cells was quantified. RA patients had a selective increase in ERK phosphorylation compared with demographically matched controls due to a mechanism distal of Ras activation. Increased ERK responses included naive and memory CD4 and CD8 T cells and did not correlate with disease activity. The augmented ERK activity delayed SHP-1 recruitment to the TCR synapse and sustained TCR-induced Zap70 and NF-kappaB signaling, facilitating responses to suboptimal stimulation. Increased responsiveness of the ERK pathway was also a characteristic finding in the SKG mouse model of RA where it preceded clinical symptoms. Treatment with subtherapeutic doses of a MEK-1/2 inhibitor delayed arthritis onset and reduced severity, suggesting that increased ERK phosphorylation predisposes for autoimmunity and can be targeted to prevent disease.
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What OpenQuestion holds
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.