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.

Human lung tissue-resident NK cells (trNK cells) are likely to play an important role in host responses towards viral infections, inflammatory conditions and cancer. However, detailed insights into these cells are still largely lacking. Here we show, using RNA sequencing and flow cytometry-based analyses, that subsets of human lung CD69 + CD16 − NK cells display hallmarks of tissue-residency, including high expression of CD49a, CD103, and ZNF683, and reduced expression of SELL, S1PR5, and KLF2/3. CD49a + CD16 − NK cells are functionally competent, and produce IFN-γ, TNF, MIP-1β, and GM-CSF. After stimulation with IL-15, they upregulate perforin, granzyme B, and Ki67 to a similar degree as CD49a − CD16 − NK cells. Comparing datasets from trNK cells in human lung and bone marrow with tissue-resident memory CD8 + T cells identifies core genes co-regulated either by tissue-residency, cell-type or location. Together, our data indicate that human lung trNK cells have distinct features, likely regulating their function in barrier immunity.

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Patients with atheromatosis in the ascending aorta had an 8.7% incidence of postoperative stroke, in spite of minor surgical modifications. The risk depended on the presence, location and extent of the disease. Randomized trials evaluating alternative surgical strategies in coronary surgery are urgently needed in high risk patients.

were employed at Astra Zeneca during parts of this study. The rest of the authors declare that they have no relevant conflicts of interest.

NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, the detailed functional capacity of human lung and peripheral blood NK cells remains to be determined in IAV and other respiratory viral infections. Here, we investigated the effects of IAV infection on human lung and peripheral blood NK cells in vitro and ex vivo following clinical infection. IAV infection of lung- and peripheral blood-derived mononuclear cells in vitro induced NK cell hyperresponsiveness to K562 target cells, including increased degranulation and cytokine production particularly in the CD56 bright CD16 − subset of NK cells. Furthermore, lung CD16 − NK cells showed increased IAV-mediated but target cell-independent activation compared to CD16 + lung NK cells or total NK cells in peripheral blood. IAV infection rendered peripheral blood NK cells responsive toward the normally NK cell-resistant lung epithelial cell line A549, indicating that NK cell activation during IAV infection could contribute to killing of surrounding non-infected epithelial cells. In vivo , peripheral blood CD56 dim CD16 + and CD56 bright CD16 − NK cells were primed during acute IAV infection, and a small subset of CD16 − CD49a + CXCR3 + NK cells could be identified, with CD49a and CXCR3 potentially promoting homing to and tissue-retention in the lung during acute infection. Together, we show that IAV respiratory viral infections prime otherwise hyporesponsive lung NK cells, indicating that both CD16 + and CD16 − NK cells including CD16 − CD49a + tissue-resident NK cells could contribute to host immunity but possibly also tissue damage in clinical IAV infection.

Although the true prevalence of distress and disorder is underestimated, the true associations between potential determinants and the outcomes seem reasonably well reproduced.

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