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Immunol."],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:p>\n                    The thymus is the primary site of T cell development, central to the establishment of self-tolerance and adaptive immune function. In mammals, the thymus undergoes age-related involution, resulting in a global decline in immune function. The thymus has some regenerative ability that relies on pre-existing thymic remnants but is insufficient to prevent involution. Here, we show that the juvenile axolotl (\n                    <jats:italic toggle=\"yes\">Ambystoma mexicanum<\/jats:italic>\n                    ) is able to regenerate its thymus de novo after complete removal, constituting an exception among vertebrates. Using single-cell transcriptomics and genetic and transplantation approaches, we demonstrate that de novo thymus regeneration results in the restoration of morphology, cell-type diversity, and function. FOXN1, although it has a conserved role in thymus organogenesis, is dispensable for the initiation of thymic regeneration. In contrast, we identify midkine signaling as a possible early driver of de novo thymus regeneration. This study demonstrates an instance of organ-level regeneration of the lymphoid system, which could guide future clinical strategies seeking to promote thymus regrowth.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adw9903","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:58:16Z","timestamp":1764961096000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Molecular basis for de novo thymus regeneration in a vertebrate, the axolotl"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-3113","authenticated-orcid":true,"given":"Anna","family":"Czarkwiani","sequence":"first","affiliation":[{"name":"Technische Universit\u00e4t Dresden, Center for Regenerative Therapies TU Dresden (CRTD), Dresden 01307, 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for Molecular Bioengineering (CMCB), TU Dresden Dresden 01307, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-2589","authenticated-orcid":true,"given":"Fabian","family":"Rost","sequence":"additional","affiliation":[{"name":"Dresden-concept Genome Center, DFG NGS Competence Center, c\/o Center for Molecular Bioengineering (CMCB), TU Dresden Dresden 01307, Germany."},{"name":"Max Planck Institute of Molecular and Cellular Biology and Genetics (MPI-CBG), Dresden 01307, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-3382","authenticated-orcid":true,"given":"Ren\u00e9","family":"Maehr","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01655, 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