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We established the steady\u2011state proteome of murine splenic pDCs directly ex vivo using deep, absolute quantitative mass spectrometry and compared it with conventional dendritic cell subsets and human pDCs. pDCs exhibited a highly conserved proteomic architecture across species, with selective divergence in central carbon metabolism, amino\u2011acid utilization, and nutrient transporter expression. Notably, pDCs expressed exceptionally high levels of the transferrin receptor (TFRC) in both mice and humans and displayed robust transferrin\u2011mediated iron uptake relative to other splenic immune populations. Despite this, pDCs did not demonstrate increased total cellular iron or enhanced ferritin\u2011based storage. Instead, proteome\u2011wide iron mapping revealed preferential allocation of iron to functional iron\u2010sulfur and heme\u2011containing proteins, particularly within mitochondrial pathways. Detection of the iron exporter ferroportin indicated coordinated iron import and efflux, establishing sustained iron flux rather than net accumulation. Functional assays showed that iron availability does not constrain TLR9\u2011induced IFN\u2011I or TNF production. Together, these data define a conserved iron\u2011handling program in pDCs characterized by high TFRC expression, balanced iron flux, and targeted redistribution into essential protein systems.<\/jats:p>","DOI":"10.1002\/eji.70219","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:17:08Z","timestamp":1781695028000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasmacytoid Dendritic Cells Exhibit High Transferrin Receptor Expression Without Iron Accumulation"],"prefix":"10.1002","volume":"56","author":[{"given":"Carrie","family":"Corkish","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology Trinity Biomedical Sciences Trinity College Dublin  Dundee Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"O'Shaughnessy","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology Trinity 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