{"id":"d0f2d300-aacd-5f6d-9e83-c35b0941dd8a","stable_key":"availability:immune-redox-and-survival:2","predicate":"can_affect","statement":"GPX4-dependent control of lipid peroxidation can affect T-cell survival in cell and animal experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Predominantly cell/animal; heterogeneous human observations and intervention findings are separate evidence categories.","direction":"context_dependent","is_public":true,"mechanism_event_id":"35f26cd7-1ecb-54b1-909a-2ac24c9651a1","mechanism_event_label":"GPX4-dependent control of lipid peroxidation can affect T-cell survival in cell and animal experiments.","subject":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"object":{"id":"8ff4d16b-06de-5ace-9ef1-2d1eeebf56cb","slug":"t-cell-survival","display_name":"T-cell survival","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"35f26cd7-1ecb-54b1-909a-2ac24c9651a1","stable_key":"availability:immune-redox-and-survival:2","event_type":"availability_dependent_change","label":"GPX4-dependent control of lipid peroxidation can affect T-cell survival in cell and animal experiments.","description":"Selenium status changes in an immune context; GPX4 perturbation studies test specific downstream defenses. Much of the detailed mechanism comes from cell and animal models; human immune findings are heterogeneous.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"condition_input","stoichiometry":null,"state_label":"Selenium status changes in an immune context; GPX4 perturbation studies test specific downstream defenses.","sequence_order":0,"notes":""},{"entity":{"id":"8ff4d16b-06de-5ace-9ef1-2d1eeebf56cb","slug":"t-cell-survival","display_name":"T-cell survival","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Selenium status changes in an immune context; GPX4 perturbation studies test specific downstream defenses.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Selenium status changes in an immune context; GPX4 perturbation studies test specific downstream defenses.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Much of the detailed mechanism comes from cell and animal models; human immune findings are heterogeneous.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A GPX4 knockout does not specify the response to dietary restriction. No single immune cascade explains every supplementation result, and no clinical immunity cutoff is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"15ae95bf-1867-5389-88d4-e605c078b7b7","evidence_kind":"source_passage","locator":"lines 358-362","start_line":358,"end_line":362,"excerpt":"T-cell subsets\n\nGPX4-dependent control of lipid peroxidation can affect survival and differentiation\n\nCell/animal","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[{"id":"97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","title":"GPX4 dependence differs between B-cell subsets and Tfh cells","kind":"contradiction","status":"corrected","why":"B-cell-specific deletion preserved measured B2/germinal-center responses while harming B1/MZ; a Tfh phenotype cannot be assigned to germinal-center B cells.","resolution":"Separate lineage-specific findings; do not infer nutritional deletion of an immune compartment in humans.","created_at":"2026-09-17 07:19:34","record_type":"correction","display_label":"Correction history","record_url":"/corrections/97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1630,"end_line":1636,"papers":[{"paper_key":"muri-b-2019","title":"B1 and Marginal Zone B Cells but Not Follicular B2 Cells Require Gpx4 to Prevent Lipid Peroxidation and Ferroptosis","url":"https://pubmed.ncbi.nlm.nih.gov/31775041/","doi":"10.1016/j.celrep.2019.10.070","year":2019,"model":"Mouse B-cell-specific Gpx4 deletion","summary":"B1/MZ vulnerable; measured follicular B2 and germinal-center responses preserved."},{"paper_key":"yao-2021","title":"Selenium-GPX4 axis protects follicular helper T cells from ferroptosis","url":"https://www.nature.com/articles/s41590-021-00996-0","doi":"10.1038/s41590-021-00996-0","year":2021,"model":"Mouse T-cell/Tfh experiments and young-adult influenza vaccination study","summary":"Narrow Tfh protection mechanism; use corrected article, author correction DOI 10.1038/s41590-024-01949-z is metadata/FACS correction, not retraction."}]},"sides":[{"conflict_id":"97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":137,"end_line":137,"quote":"| **Germinal center B**                     | lost → no affinity maturation                                              | vitamin E                            |","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","ordinal":1,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":158,"end_line":158,"quote":"**Selenium deficiency silently deletes an entire arm of innate humoral immunity**, and nothing in a standard immune workup would show it.","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","ordinal":2,"label":"Original preserved statement","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":350,"end_line":394,"quote":"Much of the detailed cell-by-cell mechanism comes from animal and cell models. These findings are biologically important but should not be converted directly into plasma cutoffs or guaranteed clinical outcomes.\n\nImmune component\n\nExperimental finding\n\nEvidence level\n\nT-cell subsets\n\nGPX4-dependent control of lipid peroxidation can affect survival and differentiation\n\nCell/animal\n\nCD8 effector responses\n\nRedox and lipid-peroxidation defenses can affect expansion/function\n\nCell/animal\n\nB-cell compartments\n\nSelenium-dependent redox systems can influence antibody responses\n\nMostly animal; some human supplementation data\n\nNeutrophils\n\nOxidative-burst biology creates high antioxidant demand\n\nCell/animal\n\nNK activity\n\nSelenium status has been associated with altered activity in some studies\n\nHuman/animal, heterogeneous\n\nMacrophage / inflammasome signaling\n\nThioredoxin, TXNIP, lipid peroxide and eicosanoid pathways provide plausible mechanisms\n\nCell/animal\n\nA useful summary is: selenium status can alter immune redox tone and cell survival, but no single immune-cell cascade explains all reported supplementation effects.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]},{"conflict_id":"97c1d4e9-b4c5-5a64-95ce-f9dc60e9d1c0","ordinal":3,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1630,"end_line":1636,"quote":"## GPX4 dependence differs between B-cell subsets and Tfh cells\n\nB-cell-specific deletion preserved measured B2/germinal-center responses while harming B1/MZ; a Tfh phenotype cannot be assigned to germinal-center B cells.\n\nSeparate lineage-specific findings; do not infer nutritional deletion of an immune compartment in humans.\nPrimary reference: [B1 and Marginal Zone B Cells but Not Follicular B2 Cells Require Gpx4 to Prevent Lipid Peroxidation and Ferroptosis](https://pubmed.ncbi.nlm.nih.gov/31775041/)\nPrimary reference: [Selenium-GPX4 axis protects follicular helper T cells from ferroptosis](https://www.nature.com/articles/s41590-021-00996-0)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":null}