Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells.
Nicole MarquardtEliisa KekäläinenPuran ChenMagda LourdaJennifer N WilsonMarlena ScharenbergPer BergmanMamdoh Al-AmeriJoanna HårdJeffrey E MoldHans-Gustaf LjunggrenJakob MichaëlssonPublished in: Nature communications (2019)
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.
Keyphrases
- nk cells
- induced apoptosis
- cell cycle arrest
- bone marrow
- flow cytometry
- gene expression
- poor prognosis
- transcription factor
- sars cov
- quality improvement
- signaling pathway
- immune response
- rheumatoid arthritis
- endoplasmic reticulum stress
- mesenchymal stem cells
- cell death
- genome wide
- squamous cell carcinoma
- neoadjuvant chemotherapy
- cell proliferation
- single cell
- artificial intelligence
- dna methylation
- machine learning
- young adults
- radiation therapy
- squamous cell
- dendritic cells
- lymph node
- big data
- emergency medicine