Nicole Marquardt1, Eliisa Kekäläinen1, Puran Chen1, Egle Kvedaraite1, Jennifer N Wilson1, Martin A Ivarsson1, Jenny Mjösberg1, Lena Berglin1, Jesper Säfholm2, Martijn L Manson3, Mikael Adner2, Mamdoh Al-Ameri4, Per Bergman4, Ann-Charlotte Orre4, Mattias Svensson1, Barbro Dahlén2, Sven-Erik Dahlén2, Hans-Gustaf Ljunggren1, Jakob Michaëlsson5. 1. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 2. Unit for Experimental Asthma and Allergy Research, Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 3. Unit for Experimental Asthma and Allergy Research, Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Respiratory, Inflammation and Autoimmunity (RIA), Innovative Medicines, Astra Zeneca R&D, Gothenburg, Sweden. 4. Thoracic Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 5. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address: jakob.michaelsson@ki.se.
Abstract
BACKGROUND: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer. OBJECTIVE: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level. METHODS: NK cells in human lung tissue and matched peripheral blood from 132 subjects were analyzed by using 16-color flow cytometry and confocal microscopy. RESULTS: CD56dimCD16+ NK cells made up the vast majority of NK cells in human lungs, had a more differentiated phenotype, and more frequently expressed educating killer cell immunoglobulin-like receptors compared with NK cells in peripheral blood. Despite this, human lung NK cells were hyporesponsive toward target cell stimulation, even after priming with IFN-α. Furthermore, we detected a small subset of NK cells expressing CD69, a marker of tissue residency. These CD69+ NK cells in the lung consisted predominantly of immature CD56brightCD16- NK cells and less differentiated CD56dimCD16+ NK cells. CONCLUSION: Here, we characterize the major NK cell populations in the human lung. Our data suggest a model in which the majority of NK cells in the human lung dynamically move between blood and the lung rather than residing in the lung as bona fide tissue-resident CD69+ NK cells.
BACKGROUND: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer. OBJECTIVE: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level. METHODS: NK cells in human lung tissue and matched peripheral blood from 132 subjects were analyzed by using 16-color flow cytometry and confocal microscopy. RESULTS: CD56dimCD16+ NK cells made up the vast majority of NK cells in human lungs, had a more differentiated phenotype, and more frequently expressed educating killer cell immunoglobulin-like receptors compared with NK cells in peripheral blood. Despite this, human lung NK cells were hyporesponsive toward target cell stimulation, even after priming with IFN-α. Furthermore, we detected a small subset of NK cells expressing CD69, a marker of tissue residency. These CD69+ NK cells in the lung consisted predominantly of immature CD56brightCD16- NK cells and less differentiated CD56dimCD16+ NK cells. CONCLUSION: Here, we characterize the major NK cell populations in the human lung. Our data suggest a model in which the majority of NK cells in the human lung dynamically move between blood and the lung rather than residing in the lung as bona fide tissue-resident CD69+ NK cells.
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