{"doi":"10.1371/journal.pbio.3003462","title":"IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin","abstract":"Red blood cell production is regulated by erythropoietin (Epo), maintaining tissue oxygen tension in the steady state and in response to stress. To date, only a handful of factors other than Epo are known to stimulate erythropoiesis, limiting therapeutic options. We recently found that IL-17, a pleiotropic pro-inflammatory cytokine, interacts synergistically with Epo to increase formation of erythroid colonies in vitro. Here, we administered IL-17 to mice to determine whether it accelerates erythropoiesis in vivo. We found that while IL-17 alone had little effect on erythroid and other hematopoietic lineages, combined treatment with both IL-17 and Epo generated a specific and strong synergistic response in erythroid progenitors that significantly increased erythropoietic rate. IL-17 administration also accelerated the erythropoietic response of mice to hypoxia. Single-cell transcriptomic analysis showed that IL-17 acts by sensitizing erythroid progenitors to Epo, rather than through a distinct transcriptional response. Using a dynamical model, we propose that this mechanism optimizes conflicting requirements in the regulation of erythropoiesis, balancing the need for low-cost maintenance of the steady state, with a sufficiently fast stress response. Further, our findings suggest a potentially broadly applicable mechanism whereby pleiotropic cytokines are able to exert lineage-specific effects when their actions are dependent on synergism with lineage-specific factors.","journal":"PLoS Biology","year":2025,"id":549416,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"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":1443620,"name":"Aishwarya Swaminathan","orcid":"0000-0001-9082-502X","position":1,"is_corresponding":false},{"id":1444117,"name":"Ashley Winward","orcid":null,"position":2,"is_corresponding":false},{"id":1444118,"name":"Logan Lalonde","orcid":null,"position":3,"is_corresponding":false},{"id":662366,"name":"Yung Hwang","orcid":"0000-0003-0098-8963","position":4,"is_corresponding":false},{"id":1376928,"name":"Noah Littman","orcid":"0000-0003-0625-395X","position":5,"is_corresponding":false},{"id":268103,"name":"Merav Socolovsky","orcid":"0000-0001-6747-7960","position":6,"is_corresponding":false},{"id":44519,"name":"Allon M. Klein","orcid":"0000-0001-8913-7879","position":7,"is_corresponding":false},{"id":1443619,"name":"Qiu Chang Wu","orcid":"0000-0003-2402-6101","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41379768","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":[]}