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Marquardt, Nicole; Kekäläinen, Eliisa; Chen, Puran; Lourda, Magda; Wilson, Jennifer N; Scharenberg, Marlena; Bergman, Per; Al-Ameri, Mamdoh; Hård, Joanna; Mold, Jeffrey E; Ljunggren, Hans-Gustaf; Michaëlsson, Jakob
Nature communications, 08/2019, Letnik: 10, Številka: 1Journal Article
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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