{"doi":"10.1016/j.brci.2025.100001","title":"Itaconate promotes the differentiation of murine stress erythroid progenitors by increasing Nrf2 activity","abstract":"• Anti-inflammatory signals promote the transition to differentiation of SEPs. • The metabolite itaconate increases nuclear factor erythroid 2–related factor 2 activity to promote the differentiation of SEPs. Steady-state erythropoiesis produces new erythrocytes at a constant rate to replace senescent erythrocytes removed in the spleen and liver. Inflammation caused by infection or tissue damage skews bone marrow hematopoiesis, increasing myelopoiesis at the expense of steady-state erythropoiesis. To compensate for the loss of production, stress erythropoiesis is induced. Stress erythropoiesis is highly conserved between mice and humans. It uses a strategy different to the constant production of steady-state erythropoiesis. Inflammatory signals promote the proliferation of immature stress erythroid progenitors (SEPs), which then commit to differentiation. This transition relies on signals made by niche macrophages in response to erythropoietin. Nitric oxide–dependent signaling drives the proliferation of SEPs, and nitric oxide production must be decreased so that progenitor cells can differentiate. Here, we show that as progenitor cells transition to differentiation, increased production of the anti-inflammatory metabolite itaconate activates nuclear factor erythroid 2–related factor 2, which decreases nitric oxide synthase 2 expression, leading to decreased nitric oxide production. Mutation of immunoresponsive gene 1, the enzyme that catalyzes the production of itaconate, causes a delayed recovery from inflammatory anemia induced by heat-killed Brucella abortus . These data show that the differentiation of SEPs relies on a switch to an anti-inflammatory metabolism and increased expression of proresolving cytokines.","journal":"Blood Red Cells & Iron","year":2025,"id":538904,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":278620,"name":"Yuanting Chen","orcid":"0000-0003-1294-479X","position":1,"is_corresponding":false},{"id":826317,"name":"Sara Trimidal","orcid":"0000-0001-5432-4439","position":2,"is_corresponding":false},{"id":1426139,"name":"Meghna Chakraborty","orcid":null,"position":3,"is_corresponding":false},{"id":726858,"name":"Aashka Shah","orcid":"0000-0003-2898-4745","position":4,"is_corresponding":false},{"id":1289127,"name":"Hangdi Gong","orcid":null,"position":5,"is_corresponding":false},{"id":239562,"name":"Imhoi Koo","orcid":"0000-0002-5816-0627","position":6,"is_corresponding":false},{"id":239567,"name":"Jingwei Cai","orcid":"0000-0002-3626-3350","position":7,"is_corresponding":false},{"id":777259,"name":"John Mcguigan","orcid":"0000-0003-4149-875X","position":8,"is_corresponding":false},{"id":777257,"name":"Molly A. Hall","orcid":"0000-0001-7740-401X","position":9,"is_corresponding":false},{"id":239569,"name":"Andrew D. Patterson","orcid":"0000-0003-2073-0070","position":10,"is_corresponding":false},{"id":350287,"name":"K. Sandeep Prabhu","orcid":"0000-0003-0644-1512","position":11,"is_corresponding":false},{"id":274990,"name":"Robert F. Paulson","orcid":"0000-0001-5923-5128","position":12,"is_corresponding":false},{"id":280175,"name":"Baiye Ruan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:25.799399Z","pmid":"40977762","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}