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Using aging mouse models, single-cell sequencing, and\n                  <jats:italic>ex vivo<\/jats:italic>\n                  organoid assays, we found that homeostatic aged AT2 cells exhibited an Interferon \u03b3 (IFN\u03b3) response associated with IFN\u03b3+ CD8+ T cells in tertiary lymphoid structures (TLS). Aged AT2 cells exhibit impaired regeneration in organoid assays and lost markers of an IFN\u03b3 response outside the lung microenvironment, demonstrating that elevated local IFN\u03b3 influences the state of AT2 cells. Neutralization of IFN\u03b3 signaling and immunoproteasome knockout mice with attenuated IFN\u03b3 levels partially rescued aged AT2 cell regeneration. Our findings demonstrate that local IFN\n                  <jats:italic>\u03b3<\/jats:italic>\n                  signaling in aging lungs actively represses alveolar regeneration, establishing chronic inflammatory signaling as a cause of age-related decline in the lung. Halting chronic inflammatory processes restored alveolar regeneration and may provide a means to improve lung health in old age.\n                <\/jats:p>","DOI":"10.64898\/2026.04.07.716929","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:50:28Z","timestamp":1775800228000},"source":"Crossref","is-referenced-by-count":1,"title":["Local IFN\u03b3 signaling contributes to the regenerative decline of aged alveolar progenitor cells"],"prefix":"10.64898","author":[{"given":"Jake","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Genetics, Harvard Medical School; Boston, MA, USA"},{"name":"Stem Cell and Regenerative Biology Program, Department of Pediatrics, Division of Hematology\/Oncology and Pulmonary Medicine, Boston Children\u2019s Hospital; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Christian Albrecht University of Kiel; Kiel, Germany"},{"name":"Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Gote-Schniering","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Department of Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland"},{"name":"Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meeta","family":"Mistry","sequence":"additional","affiliation":[{"name":"Harvard Chan Bioinformatics Core, Harvard T.H. 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