Distinguishing Human Peripheral Blood NK Cells from CD56 dim CD16 dim CD69 + CD103 + Resident Nasal Mucosal Lavage Fluid Cells

Natural killer (NK) cells are members of the innate lymphoid cells group 1 (ILC1s), which play a critical role in innate host defense against viruses and malignancies. While many studies have examined the role of circulating peripheral blood (PB) CD56 + NK cells, little is known about the resident CD56 + cell population. Therefore, matched CD56 + cells from nasal lavage fluid (NLF) and PB of smokers and non-smokers were compared phenotypically, via flow cytometry, and functionally, via NK-cell specific gene expression. NLF and PB CD56 + cells had similar expression of CD56, but differentially expressed tissue residency (CD69 and CD103) and cytotoxicity (CD16) markers. In addition, NLF CD56 dim cells expressed lower levels of cytotoxicity-associated genes, perforin ( PRF1 ) and granzyme B ( GZMB ), and increased levels of cytokines and cell signaling molecules, TRAIL , IFNGR2 , and IL8 , as compared to PB CD56 dim cells. In smokers, ITGA2 was downregulated in NLF CD56 dim cells, while markers of cytotoxic function were primarily downregulated in PB CD56 dim NK cells. Overall, NLF CD56 dim cells are a unique cell population that likely play a role in orchestrating innate immune responses in the nasal cavity, which is distinct from their role as a non-antigen-restricted cytotoxic CD56 dim lymphocytes in the PB.