Mapping human natural killer cell development in tonsil
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Secondary lymphoid tissue, including tonsil, supports human NK cell development, but the spatial organization and tissue niches that drive this differentiation remain undefined. Here, we used single cell analysis of cyclic immunofluorescence to generate a comprehensive atlas of human NK cell development in tonsil. By integrating regional localization, chemokine signaling, cytokine availability, and cell phenotype, we show that NK cell differentiation follows a reproducible spatial trajectory defined by stage-specific cell-cell interactions. CD34+ NK cell progenitors are found in the interfollicular domain in proximity to high endothelial venules, consistent with this route of progenitor entry into tissue. Mature NK cells are primarily found in the T cell-rich parafollicular domain, where they interact with other NK cells and T cell subsets. Local inflammation increases NK cell frequency in tissue through both proliferation of NK progenitors and increased frequency of mature NK cells. Finally, we identify a subset of tonsil stromal cells that support differentiation of NK cells in vitro and proliferation of NK precursors in situ. Together, these findings demonstrate that spatial localization defines human NK cell development and provide an in situ definition of niches that support human NK cell differentiation in tonsil.
Authors 15
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Columbia University Irving Medical Center
Affiliation as printed
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032
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Janine E. Melsen Aachen Department of Immunology, Leiden University Medical Center Laboratory for Pediatric Immunology
Leiden University Medical Center · Willem-Alexander Kinderziekenhuis
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands
Laboratory for Pediatric Immunology, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands
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The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · The Ohio State University
Affiliation as printed
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210
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Affiliation as printed
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, 10065
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Austrian Academy of Sciences · CeMM Research Center for Molecular Medicine · Ludwig Boltzmann Institute for Network Medicine at the University of Vienna
Affiliation as printed
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, 1090, Vienna, Austria
Ludwig Boltzmann Institute for Network Medicine at the University of Vienna, Augasse 2-6, Vienna, A-1090, Austria
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The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · The Ohio State University
Affiliation as printed
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210
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Columbia University Irving Medical Center · Columbia University
Affiliation as printed
Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 10032
Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, 10032
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Columbia University Irving Medical Center
Affiliation as printed
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032
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Columbia University Irving Medical Center · Herbert Irving Comprehensive Cancer Center · Columbia University
Affiliation as printed
Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, 10032
Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, 10032
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, 10032
Program for Mathematical Genomics, Columbia University, New York, NY, 10032
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Columbia University Irving Medical Center · Columbia University
Affiliation as printed
Department of Otolaryngology - Head and Neck Surgery, Columbia University Medical Center, New York, New York 10032
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Columbia University Irving Medical Center · Columbia University
Affiliation as printed
Department of Pediatrics, Division of Pediatric Critical Care and Hospital Medicine, Columbia University Irving Medical Center, New York, NY 10024
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Affiliation as printed
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10065
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The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · The Ohio State University
Affiliation as printed
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210
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Tisch Cancer Institute · Icahn School of Medicine at Mount Sinai
Affiliation as printed
Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029
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Columbia University Irving Medical Center
Affiliation as printed
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York NY 10032
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