Myeloid cells最新文献

{"title":"Scalable generation of pure CD103⁺ cDC1 from iDC1 cultures.","authors":"Sukriti Sharma, Fiona Flynn, Brian Capaldo, Ronald Holewinski, Qingrong Chen, Daoud Meerzaman, Thorkell Andresson, Christian T Mayer","doi":"10.70401/mc.2026.0012","DOIUrl":"10.70401/mc.2026.0012","url":null,"abstract":"<p><strong>Aims: </strong>Conventional type 1 dendritic cells (cDC1) specialize in cross-presentation and interleukin-12 production and are critical for immunity against intracellular pathogens and tumors, but remain rare <i>in vivo</i>, limiting mechanistic and translational studies. Existing bone marrow-derived dendritic cell (BMDC) methods do not achieve selective enrichment of cDC1 or scalable production at high purity. We therefore aimed to establish a high-efficiency BMDC culture system for selective generation of CD103+ cDC1 from mouse bone marrow.</p><p><strong>Methods: </strong>Mouse bone marrow cells were cultured in defined medium with recombinant FLT3L, low-dose GM-CSF, and Kit ligand (KitL) to generate induced cDC1 (iDC1). Phenotypic, transcriptomic, proteomic, phospho-proteomic, and functional analyses were performed and compared with established BMDC methods and <i>ex vivo</i> immune cell populations.</p><p><strong>Results: </strong>iDC1 cultures enabled scalable generation of an estimated 1.5 × 10⁹ CD103⁺ cDC1 at greater than 95% purity from a single mouse, representing at least a 75-fold increase relative to previous recombinant cytokine-based methods. iDC1 closely aligned with the cDC1 lineage while distinct from macrophages. Functionally, iDC1 responded robustly to innate stimulation, secreted IL-12p40 and inflammatory chemokines, and efficiently cross-presented cell-associated antigen to CD8⁺ T cells. Mechanistically, KitL and GM-CSF cooperated during early cDC1 generation, whereas GM-CSF promoted proliferation and survival during later stages of culture. iDC1 generation depended on the +32 kb <i>Irf8</i> enhancer, and STAT5- and BRD4-associated regulatory programs contributed to efficient iDC1 generation.</p><p><strong>Conclusion: </strong>iDC1 cultures are a scalable platform for studying cDC1 biology and may facilitate development and preclinical evaluation of cDC1-based immunotherapeutic strategies.</p>","PeriodicalId":524260,"journal":{"name":"Myeloid cells","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}