Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood
| Autor: | Brownlie, Demi, Scharenberg, Marlena, Mold, Jeff E., Hard, Joanna, Kekäläinen, Eliisa, Buggert, Marcus, Nguyen, Son, Wilson, Jennifer N., Al-Ameri, Mamdoh, Ljunggren, Hans-Gustaf, Marquardt, Nicole, Michaelsson, Jakob |
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| Přispěvatelé: | Medicum, HUSLAB, Department of Bacteriology and Immunology, TRIMM - Translational Immunology Research Program, University of Helsinki, Helsinki University Hospital Area |
| Rok vydání: | 2021 |
| Předmět: |
EXPRESSION
Lung Neoplasms PROMOTES GRANZYME-H Integrin alpha1 adaptive NK cells IMMUNITY Biological Sciences Flow Cytometry CYTOMEGALOVIRUS-INFECTION Adaptation Physiological Immunophenotyping memory Killer Cells Natural Immunology and Inflammation CMV INFECTION T-CELLS VIRUS Humans 3111 Biomedicine tissue-resident Lung |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance Respiratory diseases are leading causes of death worldwide. However, the local immune cell composition in the human lung and individual outliers within the population still remain largely undescribed. We here identify adaptive-like NK cell expansions with tissue-resident traits in lung and blood in approximately 20% of individuals. This particular NK cell subset, which differed from adaptive-like CD16+ blood NK cells, was hyperresponsive to target cell stimulation. Individuals with such in vivo-primed, expanded NK cells will likely experience a different course of acute lung disease such as viral infections. Furthermore, we believe that target cell-hyperresponsive tissue-resident NK cells represent a future tool in the treatment of lung cancer. Human adaptive-like “memory” CD56dimCD16+ natural killer (NK) cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated in recent years and are currently explored as a treatment strategy for hematological cancers. However, treatment of solid tumors remains limited due to insufficient NK cell tumor infiltration, and it is unknown whether large expansions of adaptive-like NK cells that are equipped for tissue residency and tumor homing exist in peripheral tissues. Here, we show that human lung and blood contains adaptive-like CD56brightCD16− NK cells with hallmarks of tissue residency, including expression of CD49a. Expansions of adaptive-like lung tissue-resident NK (trNK) cells were found to be present independently of adaptive-like CD56dimCD16+ NK cells and to be hyperresponsive toward target cells. Together, our data demonstrate that phenotypically, functionally, and developmentally distinct subsets of adaptive-like NK cells exist in human lung and blood. Given their tissue-related character and hyperresponsiveness, human lung adaptive-like trNK cells might represent a suitable alternative for therapies targeting solid tumors. |
| Databáze: | OpenAIRE |
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