ArticleJournal of neuroinflammation2015
STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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
34 citing papers in PubMed, 63 citations in OpenAlex.
- Artesunate ameliorates experimental autoimmune uveitis by inhibiting the LCN2-STAT3 axis and suppressing microglial activation.Redox report : communications in free radical research · 2026Article
- Enhanced HIF-1α cooperation by a human RORγt mutant potentiates Th17 pathogenicity.Cell reports · 2026Article
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- IL-Mediated Macrophage Polarization Axis: From Inflammatory Positive Feedback Loop to Precision Biomarkers and Therapeutic Targets for Allergic Rhinitis-A Narrative Review.Journal of asthma and allergy · 2026Review
- Biomarkers for myelin oligodendrocyte glycoprotein-associated disease: recent advances and future.Frontiers in immunology · 2026Review
- GM-CSFTheranostics · 2025Review
- Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis.International journal of molecular sciences · 2024Review
- An IL-23-STAT4 pathway is required for the proinflammatory function of classical dendritic cells during CNS inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- BHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis.ImmunoHorizons · 2023Article
- Intrinsic STAT4 Expression Controls Effector CD4 T Cell Migration and Th17 Pathogenicity.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review.Frontiers in immunology · 2023Review
- High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Landscape of alterations in the checkpoint system in myelodysplastic syndrome and implications for prognosis.PloS one · 2022Article
- TNF plays a crucial role in inflammation by signaling via T cell TNFR2.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Enhancer RNA lnc-CES1-1 inhibits decidual cell migration by interacting with RNA-binding protein FUS and activating PPARγ in URPL.Molecular therapy. Nucleic acids · 2021Article
- Recent Updates in the Immunopathology of Type 3 Immunity-Mediated Enthesitis.Current rheumatology reports · 2021Review
- Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences.Biomedicines · 2020Review
- Dimethyl itaconate, an itaconate derivative, exhibits immunomodulatory effects on neuroinflammation in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2020Article
- GM-CSF: A Promising Target in Inflammation and Autoimmunity.ImmunoTargets and therapy · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, mice genetically deficient in the transcription factor signal transducer and activator of transcription 4 (STAT4) are resistant to disease. In contrast, deletion or inhibition of the Th1-associated cytokines IL-12 or IFNγ which act upstream and downstream of STAT4, respectively, does not ameliorate disease. These discordant findings imply that STAT4 may act in a non-canonical role during EAE. Recently, STAT4 has been shown to regulate GM-CSF production by CD4 T cells and this cytokine is necessary for the induction of EAE. However, it is not known if STAT4 controls GM-CSF production by both Th1 and Th17 effector CD4 T cells.
methodsThis study utilized the MOG(35-55) peptide immunization model of EAE. Intracellular cytokine staining and novel mixed bone marrow chimeric mice were used to study the CD4 T cell-intrinsic role of STAT4 during disease. STAT4 chromatin-immunoprecipitation (ChIP-PCR) experiments were performed to show STAT4 directly interacts with the Csf2 gene loci.
resultsHerein, we demonstrate that STAT4 controls CD4 T cell-intrinsic GM-CSF production by both Th1 and Th17 CD4 T cells during EAE as well as in vitro. Importantly, we show that STAT4 interacts with the Csf2 locus in MOG(35-55)-activated effector CD4 T cells demonstrating direct modulation of GM-CSF.
conclusionsOverall, these studies illustrate a previously unrecognized role of STAT4 to regulate GM-CSF production by not only Th1 cells, but also Th17 effector CD4 T cell subsets during EAE pathogenesis. Critically, these data highlight for the first time that STAT4 is able to modulate the effector profile of Th17 CD4 T cell subsets, which redefines our current understanding of STAT4 as a Th1-centric factor.
Indexed as
Identifiers
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.