z-logo
open-access-imgOpen Access
Expression of the inhibitory receptor NKG2A correlates with increased liver and splenic NK cell response to activating receptor engagement
Author(s) -
Meyer Claire E.,
Key Phillip N.,
Zhu Toby,
Shabsovich Mark,
Ni Ann,
Tripathy Sandeep K.
Publication year - 2017
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.156
Subject(s) - degranulation , lymphokine activated killer cell , interleukin 12 , biology , cytokine , receptor , interleukin 21 , janus kinase 3 , immune system , immunology , microbiology and biotechnology , t cell , cytotoxic t cell , in vitro , biochemistry
Natural killer (NK) cells play a critical role in the innate immune response to viruses and tumors, and comprise a large proportion of the hepatic lymphocyte population. They must remain tolerant to non‐pathogenic antigens while protecting the host from harmful agents. Herein, we investigate how the NK cell response to activation receptor engagement is altered in the liver. Methods In this study, we assess IFN‐γ production and degranulation of splenic NK cells and selected subsets of liver NK cells. Flow cytometry (FCM) was used to asses IFN‐γ production and degranulation following stimulation of the NK cells with plate bound antibodies to activating receptors. Results We show that smaller percentages of hepatic NK cells produce interferon (IFN)–γ and/or degranulate than do splenic NK cells upon stimulation through activating receptors. We also found that smaller percentages of the circulating NK (cNK) cells in the liver produce IFN‐γ and/or degranulate, compared to the liver tissue resident NK (trNK) cells. In addition, IFN‐γ production by liver cNK cells is not increased in IL‐10 deficient mice, suggesting that their hyporesponsiveness is not mediated by the presence of this anti‐inflammatory cytokine in the hepatic microenvironment. On the other hand, liver trNK cells express higher levels of the inhibitory receptor NKG2A than do cNK cells, correlating with their increased IFN‐γ production and degranulation. Conclusions Liver cNK cells’ hyporesponsiveness to stimulation through activating receptors is independent of IL‐10, but correlates with decreased NKG2A expression compared to trNK cells. In addition, we demonstrate that liver NK cells become further hyporesponsive upon continuous engagement of an activating receptor on their cell surface.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here