Englander Institute for Precision Medicine

Mapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy.

TitleMapping human natural killer cell development in pediatric tonsil by imaging mass cytometry and high-resolution microscopy.
Publication TypeJournal Article
Year of Publication2023
AuthorsHegewisch-Solloa E, Melsen JE, Ravichandran H, Rendeiro AF, Freud AG, Mundy-Bosse B, Melms JC, Eisman SE, Izar B, Grunstein E, Connors TJ, Elemento O, Horowitz A, Mace EM
JournalbioRxiv
Date Published2023 Sep 06
Abstract

Natural killer (NK) cells develop from CD34+ progenitors in a stage-specific manner defined by changes in cell surface receptor expression and function. Secondary lymphoid tissues, including tonsil, are sites of human NK cell development. Here we present new insights into human NK cell development in pediatric tonsil using cyclic immunofluorescence and imaging mass cytometry. We show that NK cell subset localization and interactions are dependent on NK cell developmental stage and tissue residency. NK cell progenitors are found in the interfollicular domain in proximity to cytokine-expressing stromal cells that promote proliferation and maturation. Mature NK cells are primarily found in the T-cell rich parafollicular domain engaging in cell-cell interactions that differ depending on their stage and tissue residency. The presence of local inflammation results in changes in NK cell interactions, abundance, and localization. This study provides the first comprehensive atlas of human NK cell development in secondary lymphoid tissue.

DOI10.1101/2023.09.05.556371
Alternate JournalbioRxiv
PubMed ID37732282
PubMed Central IDPMC10508773
Grant ListR37 CA258829 / CA / NCI NIH HHS / United States
T32 CA203702 / CA / NCI NIH HHS / United States
R01 AI137073 / AI / NIAID NIH HHS / United States
R01 CA266446 / CA / NCI NIH HHS / United States
F31 AI164869 / AI / NIAID NIH HHS / United States

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