{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:47:45Z","timestamp":1791002865432,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The retinoic-acid-receptor-related orphan receptor gamma t (ROR\u03b3t) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express ROR\u03b3t. This study maps the presence of ROR\u03b3t cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By combining multicolor flow cytometry, RNAseq of peripheral blood cells, analysis of lymph node scRNAseq datasets, and microscopic analysis on human tissue sections and single-cell suspensions, this study maps the presence of ROR\u03b3t cells with DC features in human tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ROR\u03b3t-DCs are found in human lymphoid organs, particularly in lymph nodes. Lymph node ROR\u03b3t-DCs are located in the interfollicular area surrounding high endothelial venules and in the marginal sinuses. In terms of phenotype, ROR\u03b3t-DCs are distinct from other nodal dendritic cells. They express PRDM16 and PIGR as well as transcripts supporting the antigen presentation machinery, while lacking stromal markers. A significant fraction of ROR\u03b3t-DCs is proliferating, suggesting local self-renewal. Moreover, most of them lack autoimmune regulator (AIRE) expression. Comparison with mouse ROR\u03b3t Thetis cells (TC) and Janus cells (JC) shows more similarity with group II TC than group I and III TC or JC, all of which are tolerogenic and express AIRE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this study identifies human lymph nodes as a relevant niche for ROR\u03b3t-DCs and establishes tools for their microscopic mapping in human disease states.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1527499","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T04:10:25Z","timestamp":1748578225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mapping of ROR\u03b3t+ dendritic cells in human tissues establishes their preferential niche in adult lymph 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