{"id":"320d4a18-cb97-5fdf-90eb-35d9f3b1d618","stable_key":"research:dc-gsh-cysteine","predicate":"provides_precursor_for","statement":"Dendritic-cell GSH secretion followed by extracellular cleavage contributes extracellular cysteine in mouse DC/T-cell coculture.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"9800e87c-32c1-50eb-aaca-06dbb6f550f8","mechanism_event_label":"Dendritic cells can supply cysteine by exporting and breaking down glutathione.","subject":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"object":{"id":"ff209c82-1f28-5bce-bfea-84f5e25251ab","slug":"extracellular-cysteine","display_name":"extracellular cysteine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"9800e87c-32c1-50eb-aaca-06dbb6f550f8","stable_key":"research:dc-gsh-cysteine","event_type":"metabolite_supply","label":"Dendritic cells can supply cysteine by exporting and breaking down glutathione.","description":"Dendritic-cell GSH secretion followed by extracellular cleavage contributes extracellular cysteine in mouse DC/T-cell coculture.","status":"active","compartment":null,"participants":[{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ff209c82-1f28-5bce-bfea-84f5e25251ab","slug":"extracellular-cysteine","display_name":"extracellular cysteine","entity_type_key":"small_molecule"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Dendritic cells and T cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse DC/T-cell cocultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Distinct from an unproven secreted TrxR1 circuit; not the sole established route in humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c88dbfbb-c539-5465-8be0-0cda829be145","evidence_kind":"curated_literature_summary","locator":"lines 1312-1322","start_line":1312,"end_line":1322,"excerpt":"## dc-gsh-cysteine\n\nDendritic cells can supply cysteine by exporting and breaking down glutathione.\n\nDendritic-cell GSH secretion followed by extracellular cleavage contributes extracellular cysteine in mouse DC/T-cell coculture.\n\nOrganism: Mus musculus\nCell type: Dendritic cells and T cells\nExperimental model: Mouse DC/T-cell cocultures\nLimitations: Distinct from an unproven secreted TrxR1 circuit; not the sole established route in humans.\nPrimary reference: [Extracellular redox modulation by regulatory T cells](https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/)","model_system":"Mouse DC/T-cell cocultures","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"244f98a6-efa9-5b0a-82ba-954c442a417c","title":"A secreted TrxR1 synaptic regeneration circuit is not established","kind":"qualification","status":"qualified","why":"Cysteine release and thioredoxin secretion do not establish an extracellular TrxR1/electron-donor circuit controlled by APC selenium.","resolution":"Retain as a hypothesis; model GSH export/cleavage separately. Reduction acts on surface disulfides to form thiols.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/244f98a6-efa9-5b0a-82ba-954c442a417c","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1622,"end_line":1628,"papers":[{"paper_key":"angelini-2002","title":"Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation","url":"https://pubmed.ncbi.nlm.nih.gov/11792859/","doi":"10.1073/pnas.022630299","year":2002,"model":"Human dendritic-cell/T-cell experiments","summary":"Documents cysteine release and antigen-dependent thioredoxin secretion, not an established extracellular TrxR1 circuit."},{"paper_key":"yan-2009","title":"Extracellular redox modulation by regulatory T cells","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/","doi":"10.1038/nchembio.212","year":2009,"model":"Mouse DC/T-cell cocultures","summary":"GSH export and extracellular cleavage provide cysteine."}]},"sides":[{"conflict_id":"244f98a6-efa9-5b0a-82ba-954c442a417c","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":118,"end_line":122,"quote":"**And APCs secrete thioredoxin-1 itself.** Extracellular Trx1 reduces **exofacial thiols** on the T cell surface — free surface cysteines that increase on activation and are required for full TCR responsiveness. Surface-associated/secreted **TrxR1** regenerates it.\n\n**So:** a selenoenzyme is operating **in the synaptic cleft**, between two cells, reducing the outer face of the T cell membrane so that the receptor can work.\n\n**Corollary:** an APC's selenium status partly determines a T cell's activation threshold. **Selenium is a paracrine signal, not just a cell-autonomous nutrient.**","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"244f98a6-efa9-5b0a-82ba-954c442a417c","ordinal":1,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1622,"end_line":1628,"quote":"## A secreted TrxR1 synaptic regeneration circuit is not established\n\nCysteine release and thioredoxin secretion do not establish an extracellular TrxR1/electron-donor circuit controlled by APC selenium.\n\nRetain as a hypothesis; model GSH export/cleavage separately. Reduction acts on surface disulfides to form thiols.\nPrimary reference: [Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation](https://pubmed.ncbi.nlm.nih.gov/11792859/)\nPrimary reference: [Extracellular redox modulation by regulatory T cells](https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]},{"id":"3ac902fa-4705-599f-bf57-3cbb0bd20efc","title":"Activated T cells can import cystine","kind":"context_difference","status":"qualified","why":"The blanket inability statement ignores activation-induced xCT uptake in human T cells.","resolution":"Separate resting from activated cells and DC glutathione supply from direct T-cell transport.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/3ac902fa-4705-599f-bf57-3cbb0bd20efc","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1614,"end_line":1620,"papers":[{"paper_key":"siska-2016","title":"Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5065394/","doi":"10.1016/j.jim.2016.08.013","year":2016,"model":"TCR-stimulated human CD4/CD8 lymphocytes","summary":"Activated cells increase xCT expression and cystine uptake."},{"paper_key":"yan-2009","title":"Extracellular redox modulation by regulatory T cells","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/","doi":"10.1038/nchembio.212","year":2009,"model":"Mouse DC/T-cell cocultures","summary":"GSH export and extracellular cleavage provide cysteine."}]},"sides":[{"conflict_id":"3ac902fa-4705-599f-bf57-3cbb0bd20efc","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":103,"end_line":103,"quote":"**T cells are metabolically crippled for cysteine.** They express little **xCT (SLC7A11)**, so they can't import cystine, and they have limited capacity to reduce it. Without cysteine there's no GSH, and without GSH the whole TCR redox cycle stalls.","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"3ac902fa-4705-599f-bf57-3cbb0bd20efc","ordinal":1,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1614,"end_line":1620,"quote":"## Activated T cells can import cystine\n\nThe blanket inability statement ignores activation-induced xCT uptake in human T cells.\n\nSeparate resting from activated cells and DC glutathione supply from direct T-cell transport.\nPrimary reference: [Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes](https://pmc.ncbi.nlm.nih.gov/articles/PMC5065394/)\nPrimary reference: [Extracellular redox modulation by regulatory T cells](https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Dendritic cells can supply cysteine by exporting and breaking down glutathione.","evidence_scope":"direct_experimental","papers":[{"key":"yan-2009","title":"Extracellular redox modulation by regulatory T cells","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2760945/","doi":"10.1038/nchembio.212","year":2009,"model":"Mouse DC/T-cell cocultures","summary":"GSH export and extracellular cleavage provide cysteine."}]}}