ArticleThe Journal of experimental medicine2024
TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed.
- STAT3-mediated suppression of the pre-induction silencer Ets-2 in activated T helper cells.Molecular biology reports · 2026Article
- Mechanisms of Therapeutic Resistance and Recent Advances in Glioblastoma Treatment.Immunology and cell biology · 2026Review
- Article
- Betulinic acid alleviates lipopolysaccharide-induced spleen injury by inhibiting the IL-17 signaling pathway in broilers.Poultry science · 2026Article
- SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.EMBO reports · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Th17/IL-17A Drives Alveolar Bone Loss via the JAK/STAT3-RANKL Axis in the Periodontal Ligament.Oral diseases · 2026Article
- ProteinJournal of pharmaceutical analysis · 2026Review
- Resident microbes shape host immunity and protect against pathogen infection and inflammatory disease.Cellular and molecular life sciences : CMLS · 2026Review
- Common crosstalk genes and molecular mechanisms in Helicobacter pylori infection and colorectal cancer.Discover oncology · 2026Article
- Role of the STAT3 Signaling Pathway in Cell Proliferation and Inflammation in Psoriasis and Approaches for Targeted Therapies: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Non-canonical IL‑22 receptor signaling remodels the oral mucosal barrier during Candida albicans immunosurveillance.Nature communications · 2026Article
- Palmitoylation Induced Activation of SMAD3 Exacerbates Colitis by Promoting Tissue-resident Memory T Cells Differentiation.Inflammation · 2026Article
- DOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells.The Journal of experimental medicine · 2026Article
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells.bioRxiv : the preprint server for biology · 2026Article
- The inhibition of miR-125b-5P prevented Treg differentiation through activating STAT3/HIF-1α pathway in PBMCs of ankylosing spondylitis.Arthritis research & therapy · 2026Article
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- CD4European journal of immunology · 2026Article
- The E3 ligases Itch and WWP2 regulate autoimmune neuroinflammation by controlling TNature communications · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
TH17 differentiation is critically controlled by "signal 3" of cytokines (IL-6/IL-23) through STAT3. However, cytokines alone induced only a moderate level of STAT3 phosphorylation. Surprisingly, TCR stimulation alone induced STAT3 phosphorylation through Lck/Fyn, and synergistically with IL-6/IL-23 induced robust and optimal STAT3 phosphorylation at Y705. Inhibition of Lck/Fyn kinase activity by Srci1 or disrupting the interaction between Lck/Fyn and STAT3 by disease-causing STAT3 mutations selectively impaired TCR stimulation, but not cytokine-induced STAT3 phosphorylation, which consequently abolished TH17 differentiation and converted them to FOXP3+ Treg cells. Srci1 administration or disrupting the interaction between Lck/Fyn and STAT3 significantly ameliorated TH17 cell-mediated EAE disease. These findings uncover an unexpected deterministic role of TCR signaling in fate determination between TH17 and Treg cells through Lck/Fyn-dependent phosphorylation of STAT3, which can be exploited to develop therapeutics selectively against TH17-related autoimmune diseases. Our study thus provides insight into how TCR signaling could integrate with cytokine signal to direct T cell differentiation.
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.