ArticleJCI insight2021
A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg balance.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Decoding the PI3K/Akt/mTOR-JAK/STAT signaling axis in multiple sclerosis: mechanistic crosstalk and therapeutic opportunities.Immunologic research · 2026Review
- SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.EMBO reports · 2026Article
- SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.bioRxiv : the preprint server for biology · 2026Article
- Irisin-Treg crosstalk: unveiling a mechanism in neural cognitive regulation.Annals of medicine · 2025Review
- The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies.International journal of molecular sciences · 2025Review
- Foxp3Research square · 2025Article
- Co-Inhibition of PARP and STAT3 as a Promising Approach for Triple-Negative Breast Cancer.Biomolecules · 2025Article
- Niclosamide Alleviated Skin Inflammation and Restored the Balance between Effector and Regulatory T Cells in Skin.Biomolecules & therapeutics · 2025Article
- Deferoxamine preconditioning of canine stem cell derived extracellular vesicles alleviates inflammation in an EAE mouse model through STAT3 regulation.Scientific reports · 2024Article
- Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates.The Journal of molecular diagnostics : JMD · 2024Article
- TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.Neuroscience bulletin · 2024Article
- MicroRNA-125a-5p regulates the effect of Tregs on Th1 and Th17 through targeting ETS-1/STAT3 in psoriasis.Journal of translational medicine · 2023Article
- Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis.Investigative ophthalmology & visual science · 2023Article
- Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages.iScience · 2022Article
- LLL12B, a Novel Small-Molecule STAT3 Inhibitor, Induces Apoptosis and Suppresses Cell Migration and Tumor Growth in Triple-Negative Breast Cancer Cells.Biomedicines · 2022Article
- Transcriptional regulatory networks of circulating immune cells in type 1 diabetes: A community knowledgebase.iScience · 2022Article
- Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function.Frontiers in immunology · 2022Review
- Perspectives of herbs and their natural compounds, and herb formulas on treating diverse diseases through regulating complicated JAK/STAT signaling.Frontiers in pharmacology · 2022Review
- Article
- Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity.Journal of neuroimmunology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Reestablishing an appropriate balance between T effector cells (Teff) and Tregs is essential for correcting autoimmunity. Multiple sclerosis (MS) is an immune-mediated chronic CNS disease characterized by neuroinflammation, demyelination, and neuronal degeneration, in which the Teff:Treg balance is skewed toward pathogenic Teffs Th1 and Th17 cells. STAT3 is a key regulator of Teff:Treg balance. Using the structure-based design, we have developed a potentially novel small-molecule prodrug LLL12b that specifically inhibits STAT3 and suppresses Th17 differentiation and expansion. Moreover, LLL12b regulates the fate decision between Th17 and Tregs in an inflammatory environment, shifting Th17:Treg balance toward Tregs and favoring the resolution of inflammation. Therapeutic administration of LLL12b after disease onset significantly suppresses disease progression in adoptively transferred, chronic, and relapsing-remitting experimental autoimmune encephalomyelitis. Disease relapses were also significantly suppressed by LLL12b given during the remission phase. Additionally, LLL12b shifts Th17:Treg balance of CD4+ T cells from MS patients toward Tregs and increases Teff sensitivity to Treg-mediated suppression. These data suggest that selective inhibition of STAT3 by the small molecule LLL12b recalibrates the effector and regulatory arms of CD4+ T responses, representing a potentially clinically translatable therapeutic strategy for MS.
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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.