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Here we used an integrated approach of dynamic human, humanized mouse and non-human primate models and sampling of efferent lymph fluid to determine recirculation and TR patterns of human NK cells. By intravascular labeling, we showed that CD56\n                    <jats:sup>bright<\/jats:sup>\n                    NK cells access tissue niches at steady state. Furthermore, in human liver transplantation, donor-derived CD56\n                    <jats:sup>bright<\/jats:sup>\n                    NK cells represent the dominant TR NK cell population early after transplantation, but are replaced over time by infiltrating recipient NK cells that establish TR traits, a process partly regulated by Runx3. Transient TR CD56\n                    <jats:sup>bright<\/jats:sup>\n                    NK cells recirculated via lymphatics, displaying a consistent phenotype detectable in draining lymph nodes and efferent lymph fluid, and waned from peripheral blood on lymph node egress blockade. Finally, CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NK cells, constrained to vasculature at steady state, entered lymph nodes upon inflammation. This study provides a mechanistic framework for the transient tissue residency and recirculation pattern of human NK cell populations.\n                  <\/jats:p>","DOI":"10.1038\/s41590-025-02290-9","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T09:02:54Z","timestamp":1760432574000},"page":"2004-2015","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Transient tissue residency and lymphatic egress define human CD56bright NK cell homeostasis"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-4346","authenticated-orcid":false,"given":"Annika","family":"Niehrs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hertwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-1719","authenticated-orcid":false,"given":"Marcus","family":"Buggert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Statzu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-4865","authenticated-orcid":false,"given":"M. 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