Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells.,Nature Communications

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Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-26 , DOI: 10.1038/s41467-019-11632-9
Nicole Marquardt ₁ , Eliisa Kekäläinen _{1,

2,

3} , Puran Chen ₁ , Magda Lourda _{1,

4} , Jennifer N Wilson ₁ , Marlena Scharenberg ₁ , Per Bergman ₅ , Mamdoh Al-Ameri ₅ , Joanna Hård ₆ , Jeffrey E Mold ₆ , Hans-Gustaf Ljunggren ₁ , Jakob Michaëlsson ₁

Affiliation

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.

中文翻译：

人肺组织驻留NK细胞中独特的转录和蛋白质表达特征。

人肺组织驻留NK细胞（trNK细胞）可能在宿主对病毒感染，炎性疾病和癌症的反应中起重要作用。但是，仍然缺少对这些细胞的详细了解。在这里，我们使用RNA测序和基于流式细胞仪的分析显示，人肺CD69 + CD16-NK细胞子集显示出组织驻留的特征，包括CD49a，CD103和ZNF683的高表达，以及SELL，S1PR5的表达降低和KLF2 / 3。CD49a + CD16-NK细胞具有功能能力，并产生IFN-γ，TNF，MIP-1β和GM-CSF。用IL-15刺激后，它们将穿孔素，颗粒酶B和Ki67上调至与CD49a-CD16-NK细胞相似的程度。将人肺和骨髓中的trNK细胞与组织驻留记忆CD8 + T细胞的数据集进行比较，可以确定通过组织驻留，细胞类型或位置共同调控的核心基因。总之，我们的数据表明人肺trNK细胞具有独特的特征，可能调节其在屏障免疫中的功能。

更新日期：2019-08-26

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