Component
STAT5
STAT5A/STAT5B signaling family; isoforms are not resolved by this curated Tfh branch.
4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What it acts on
Sustained STAT5 activity inhibited BCL6-associated Tfh differentiation in the studied model.
Experimental context and source evidence
- cell_type
- transferred antigen-specific CD4 T cells
- experimental_model
- LCMV infection
- limitations
- Not all IL-2 effects are inhibitory.
- organism
- mouse
Selenium: literature corrections and mechanism additions · lines 930–940
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · LCMV infection · secondary_verified · secondary_verified
## stat5-inhibits-tfh-differentiation More STAT5 signaling reduced the Tfh cell fate. Sustained STAT5 activity inhibited BCL6-associated Tfh differentiation in the studied model. Organism: mouse Cell type: transferred antigen-specific CD4 T cells Experimental model: LCMV infection Limitations: Not all IL-2 effects are inhibitory. Primary reference: [STAT5 is a potent negative regulator of TFH cell differentiation](https://pmc.ncbi.nlm.nih.gov/articles/PMC3281266/)
Complete structured claim and evidence
What acts on it
IL-2 signaling activates STAT5 in the studied CD4 T-cell differentiation context.
Experimental context and source evidence
- cell_type
- antigen-specific CD4 T cells
- experimental_model
- LCMV infection and signaling perturbations
- limitations
- No selenium intervention in this study.
- organism
- mouse
Selenium: literature corrections and mechanism additions · lines 918–928
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · LCMV infection and signaling perturbations · secondary_verified · secondary_verified
## il2-activates-stat5-tfh-context IL-2 engages a signal that can oppose Tfh development. IL-2 signaling activates STAT5 in the studied CD4 T-cell differentiation context. Organism: mouse Cell type: antigen-specific CD4 T cells Experimental model: LCMV infection and signaling perturbations Limitations: No selenium intervention in this study. Primary reference: [STAT5 is a potent negative regulator of TFH cell differentiation](https://pmc.ncbi.nlm.nih.gov/articles/PMC3281266/)
Complete structured claim and evidence
Where it participates (unsigned role)
Human T cells exposed to tumor supernatants lost H3K79 methylation; adding methionine to human colorectal tumor-infiltrating T-cell cultures improved H3K79me2 and STAT5 readouts.
Experimental context and source evidence
- availability_state
- nutrient_deficiency Imported condition classification; unverified.
- evidence_access
- Primary full text
- experimental_model
- Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m.
- limitations
- A defined histone mark is not a global DNA methylation readout; not a validated oral cancer treatment. Correction record: Author correction published online 12 December 2025 (2026 issue): Extended Data Fig. 1j originally duplicated the A375-supernatant flow-cytometry plot in the Sup+Ser condition; publisher replaced the representative image. This is a figure correction, not an opposing scientific finding. https://www.nature.com/articles/s41586-025-09845-8
- nutrient_topic
- L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
- plain_language
- Nutrient competition reached a specific chromatin and signaling program.
- primary_references
- Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32879489/ · DOI 10.1038/s41586-020-2682-1
- trigger_kind
- nutrient_deficiency Imported condition classification; unverified.
L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 436–442
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m. · source_derived_draft · unverified_draft
## methionine-tcell-histone-stat5 Nutrient competition reached a specific chromatin and signaling program. Human T cells exposed to tumor supernatants lost H3K79 methylation; adding methionine to human colorectal tumor-infiltrating T-cell cultures improved H3K79me2 and STAT5 readouts. Model: Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m. Limitations: A defined histone mark is not a global DNA methylation readout; not a validated oral cancer treatment. Correction record: Author correction published online 12 December 2025 (2026 issue): Extended Data Fig. 1j originally duplicated the A375-supernatant flow-cytometry plot in the Sup+Ser condition; publisher replaced the representative image. This is a figure correction, not an opposing scientific finding. https://www.nature.com/articles/s41586-025-09845-8 Evidence access: Primary full text Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32879489/ · DOI 10.1038/s41586-020-2682-1
Complete structured claim and evidenceBlimp-1 deletion relieved STAT5-mediated inhibition of Tfh differentiation.
Experimental context and source evidence
- cell_type
- antigen-specific CD4 T cells
- experimental_model
- Conditional Prdm1 deletion with active STAT5
- limitations
- Dependency does not prove direct STAT5 induction of PRDM1.
- organism
- mouse
Selenium: literature corrections and mechanism additions · lines 942–952
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Conditional Prdm1 deletion with active STAT5 · secondary_verified · secondary_verified
## blimp1-required-for-stat5-tfh-inhibition STAT5's inhibitory effect depended substantially on Blimp-1. Blimp-1 deletion relieved STAT5-mediated inhibition of Tfh differentiation. Organism: mouse Cell type: antigen-specific CD4 T cells Experimental model: Conditional Prdm1 deletion with active STAT5 Limitations: Dependency does not prove direct STAT5 induction of PRDM1. Primary reference: [STAT5 is a potent negative regulator of TFH cell differentiation](https://pmc.ncbi.nlm.nih.gov/articles/PMC3281266/)
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.