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<p>Human tissue-resident (TR) CD56<sup>bright</sup> natural killer (NK) cells can be identified by expression of integrins and chemokine receptors inferred from murine studies, but many aspects of their homeostasis are unclear. 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<sup>bright</sup> NK cells access tissue niches at steady state. Furthermore, in human liver transplantation, donor-derived CD56<sup>bright</sup> 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<sup>bright</sup> 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<sup>dim</sup> 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.</p>

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Transient tissue residency and lymphatic egress define human CD56bright NK cell homeostasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Annika Niehrs,
  • Laura Hertwig,
  • Marcus Buggert,
  • Isabella Nordström,
  • Maura Statzu,
  • M. Betina Pampena,
  • Sadia Samer,
  • James J. Knox,
  • Benedikt Strunz,
  • Dan Sun,
  • Son Nguyen,
  • Claudia Janoschka,
  • Yafei Xing,
  • Vincent H. Wu,
  • Ernesto Sparrelid,
  • Arlisa Alisjahbana,
  • Yu Gao,
  • Natalie Sleiers,
  • Otto Strauss,
  • Iva Filipovic,
  • Andrea Ponzetta,
  • Itzel Medina-Andrade,
  • Vera Nilsén,
  • Carl Jorns,
  • Martin Cornillet,
  • Christopher Maucourant,
  • Christoph Ziegenhain,
  • Julia Hengst,
  • George Tweet,
  • Kyle Kroll,
  • Gregory J. Golden,
  • Heiner Wedemeyer,
  • Murat Kürtüncü,
  • Yoav Dori,
  • Maxim G. Itkin,
  • Luisa Klotz,
  • Marie Schaffer,
  • Bo-Göran Ericzon,
  • Martin A. Ivarsson,
  • Mirko Paiardini,
  • Greg Nowak,
  • Tim Willinger,
  • R. Keith Reeves,
  • Michael R. Betts,
  • Niklas K. Björkström

摘要

Human tissue-resident (TR) CD56bright natural killer (NK) cells can be identified by expression of integrins and chemokine receptors inferred from murine studies, but many aspects of their homeostasis are unclear. 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 CD56bright NK cells access tissue niches at steady state. Furthermore, in human liver transplantation, donor-derived CD56bright 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 CD56bright 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, CD56dim 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.