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Immunol."],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:p>\n                    Effective pulmonary immunity requires the precise spatial organization of immune cells, yet the mechanisms guiding their intratissue positioning during inflammation remain unclear. Here, we identify a cholesterol-derived chemotactic axis that spatially organizes T helper 2 (T\n                    <jats:sub>H<\/jats:sub>\n                    2) cells during fungal-induced pulmonary type 2 inflammation. Inflammation-expanded macrophages expressing cholesterol-25-hydroxylase (CH25H) produced 25-hydroxycholesterol, which was converted into the oxysterol 7\u03b1,25-dihydroxycholesterol to attract GPR183-expressing T\n                    <jats:sub>H<\/jats:sub>\n                    2 cells into infectious lesions. This T\n                    <jats:sub>H<\/jats:sub>\n                    2 cell positioning suppressed interferon-\u03b3 responsiveness in inflammatory Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, promoting fungal persistence. Disruption of this axis via T\n                    <jats:sub>H<\/jats:sub>\n                    2-specific GPR183 deletion restored type 1 macrophage activation and enhanced fungal clearance. Our findings reveal a macrophage-driven, metabolite-based mechanism of immunosuppressive cell positioning in inflamed lung tissue.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aee0990","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:00:46Z","timestamp":1784311246000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage-derived oxysterols organize T helper 2 cells to suppress type 1 inflammation during pulmonary fungal infection"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4827-6191","authenticated-orcid":true,"given":"Yufan","family":"Zheng","sequence":"first","affiliation":[{"name":"Molecular Mycology and Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, 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Health, Bethesda, MD 20892, USA."},{"name":"Department of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7496-9073","authenticated-orcid":true,"given":"Lillian B.","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Molecular Mycology and Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-9873","authenticated-orcid":true,"given":"Chinaemerem U.","family":"Onyishi","sequence":"additional","affiliation":[{"name":"Molecular Mycology and Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National 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Schlitzer GPR183 targets lung-resident CD301b+ conventional dendritic cells type 2 to a subtissular TSLP\u2013TSLP receptor mediated survival niche within the adventital cuff. bioRxiv 505379 [Preprint] (2022). https:\/\/doi.org\/10.1101\/2022.08.28.505379.","DOI":"10.1101\/2022.08.28.505379"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109204"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01121-x"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100022"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.240093.118"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10394"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0156-4"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.aee0990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:00:48Z","timestamp":1784311248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.aee0990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":83,"journal-issue":{"issue":"121","published-print":{"date-parts":[[2026,7,17]]}},"alternative-id":["10.1126\/sciimmunol.aee0990"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.aee0990","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaee0990"}}