Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells

Nicole Marquardt (), Eliisa Kekäläinen, Puran Chen, Magda Lourda, Jennifer N. Wilson, Marlena Scharenberg, Per Bergman, Mamdoh Al-Ameri, Joanna Hård, Jeffrey E. Mold, Hans-Gustaf Ljunggren and Jakob Michaëlsson
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Nicole Marquardt: Karolinska University Hospital
Eliisa Kekäläinen: Karolinska University Hospital
Puran Chen: Karolinska University Hospital
Magda Lourda: Karolinska University Hospital
Jennifer N. Wilson: Karolinska University Hospital
Marlena Scharenberg: Karolinska University Hospital
Per Bergman: Karolinska University Hospital
Mamdoh Al-Ameri: Karolinska University Hospital
Joanna Hård: Karolinska Institutet
Jeffrey E. Mold: Karolinska Institutet
Hans-Gustaf Ljunggren: Karolinska University Hospital
Jakob Michaëlsson: Karolinska University Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11632-9

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