Trial reportThe Journal of clinical investigation2014
CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 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
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- The dual role of mTOR in multiple sclerosis pathophysiology: a systematic review.Journal of neurology · 2026Pooled it
- GPCR-Driven Muscarinic M1 and Histamine H1 Receptor Signaling Converging on the PI3K/Akt/mTOR Pathway: Functional Integration in Neuroinflammation and Myelin Repair in Multiple Sclerosis.Molecular neurobiology · 2026Review
- Reinvigorating CD8Journal of nanobiotechnology · 2026Article
- DNA methylation variability in pediatric aplastic anaemia contributes to T-cell differentiation.Clinical and translational medicine · 2026Article
- The landscape of cellular immune alteration in systemic lupus erythematosus.Frontiers in immunology · 2026Review
- Autoimmune disease risk gene ANKRD55 promotes TH17 effector function through metabolic modulation.The Journal of experimental medicine · 2025Article
- Immunomodulation of behavior impairment via spleen-specific targeting lipid nanoparticles in a MeCP2 transgenic mouse model.Scientific reports · 2025Article
- IL-17ACR open rheumatology · 2025Article
- EPHX1 enhances drug resistance to regorafenib by activating the JAK/STAT signaling pathway in hepatocellular carcinoma cell lines.Hereditas · 2025Article
- Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Impact of immune cell metabolism on membranous nephropathy and prospective therapy.Communications biology · 2025Review
- Immunometabolism of Tregs: mechanisms, adaptability, and therapeutic implications in diseases.Frontiers in immunology · 2025Review
- Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Nanovesicles Alleviated Colitis via Modulating Th17/Treg Balance Through Hsa-miR-27b-3p-Mediated Suppression of PI3K/AKT/STAT3 Signaling Pathway.International journal of nanomedicine · 2025Article
- Metabolic reprogramming as a therapeutic target for modulating the Th17/Treg balance in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
- The Role of Podocytes in Lupus Pathology.Current rheumatology reports · 2024Review
- Systemic lupus erythematosus: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- Dynamics of CD4+ and CD8+ Lymphocytic Inflammatory Infiltrates in Lupus Nephritis.International journal of molecular sciences · 2024Article
- Article
- CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses.Nature communications · 2024Article
- Immune imbalance in Lupus Nephritis: The intersection of T-Cell and ferroptosis.Frontiers in immunology · 2024Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Tissue inflammation in several autoimmune diseases, including SLE and MS, has been linked to an imbalance of IL-17-producing Th (Th17) cells and Tregs; however, the factors that promote Th17-driven autoimmunity are unclear. Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Isolation of naive T cells from a murine model of lupus revealed increased levels of CaMK4 following stimulation with Th17-inducing cytokines but not following Treg, Th1, or Th2 induction. Furthermore, naive T cells from mice lacking CaMK4 did not produce IL-17. Genetic or pharmacologic inhibition of CaMK4 decreased the frequency of IL-17-producing T cells and ameliorated EAE and lupus-like disease in murine models. Inhibition of CaMK4 reduced Il17 transcription through decreased activation of the cAMP response element modulator α (CREM-α) and reduced activation of the AKT/mTOR pathway, which is known to enhance Th17 differentiation. Importantly, silencing CaMK4 in T cells from patients with SLE and healthy individuals inhibited Th17 differentiation through reduction of IL17A and IL17F mRNA. Collectively, our results suggest that CaMK4 inhibition has potential as a therapeutic strategy for Th17-driven autoimmune diseases.
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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.