{"doi":"10.4049/jimmunol.2400292","title":"Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis","abstract":"Vitamin D status, the vitamin D receptor (VDR), and the ability to produce active vitamin D [1,25(OH)2D, regulated by Cyp27b1] regulate fetal and adult hematopoiesis. Transgenic reporter mice that express the tdTomato RFP as an indication of Vdr expression were used to identify immune cells that express the Vdr. Vdr/tdTomato+ hematopoietic progenitors were identified as early as embryonic day (E)15.5, establishing that these cells have expressed the Vdr and are vitamin D targets. Maternal vitamin D deficiency [D-; serum 25(OH)D < 20 ng/ml] or Vdr knockout or Cyp27b1 knockout resulted in embryos with fewer fetal progenitors. Vdr/tdTomato+ expression was found to increase with age in CD8+ T cells and innate lymphoid cells (ILCs)1 and ILC3, suggesting that initial Vdr expression in these cells is dependent on environmental factors immediately postbirth. In adult tissues, the frequencies of mature T cells and ILCs as well as Vdr/tdTomato expression were reduced by D-. Maternal D- resulted in fewer progenitors that expressed Vdr/tdTomato+ at E15.5 and fewer Vdr/tdTomato+ immune cells in the adult spleen than offspring from D+ mice. We challenged D- mice with H1N1 influenza infection and found that D- mice were more susceptible than D+ mice. Treating D- mice with vitamin D restored Vdr/tdTomato+ expression in splenic T cells and partially restored resistance to H1N1 infection, which shows that developmental D- results in lingering effects on Vdr expression in the adult immune system that compromise the immune response to H1N1 infection. Vitamin D and the Vdr regulate hematopoiesis in both fetal and postnatal phases of immune cell development that impact the immune response to a viral infection.","journal":"The Journal of Immunology","year":2024,"id":447550,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":906454,"name":"Nicole E. Froelich","orcid":null,"position":1,"is_corresponding":false},{"id":1266162,"name":"Mengzhu Tang","orcid":null,"position":2,"is_corresponding":false},{"id":385656,"name":"Veronika Weaver","orcid":"0000-0002-3558-7660","position":3,"is_corresponding":false},{"id":274990,"name":"Robert F. Paulson","orcid":"0000-0001-5923-5128","position":4,"is_corresponding":false},{"id":386644,"name":"Margherita T. Cantorna","orcid":null,"position":5,"is_corresponding":false},{"id":385655,"name":"Juhi Arora","orcid":"0000-0002-2356-0559","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:02:03.354708Z","pmid":"39320233","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":[]}