Stage-specific regulation of natural killer cell homeostasis and response against viral infection by microRNA-155

Natural killer (NK) cells function in the recognition and destruction of host cells infected with pathogens. Many regulatory mechanisms govern the potent responses of NK cells, both at the cellular and molecular level. Ablation of microRNA (miRNA) processing enzymes demonstrated that miRNAs play cri...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (17), p.6967-6972
Main Authors: Zawislak, Carolyn L., Beaulieu, Aimee M., Loeb, Gabriel B., Karo, Jenny, Canner, David, Bezman, Natalie A., Lanier, Lewis L., Rudensky, Alexander Y., Sun, Joseph C.
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Biological Sciences
Cells
Chromatin Immunoprecipitation
Cytokines
Enzymes
Gene Deletion
Gene expression regulation
Gene Expression Regulation - immunology
Herpesviridae Infections - immunology
Homeostasis
Homeostasis - immunology
Infections
Interleukin-12 - metabolism
Interleukin-18 - metabolism
Killer Cells, Natural - immunology
Liver
Luciferases
Mice
MicroRNA
MicroRNAs - genetics
MicroRNAs - metabolism
Muromegalovirus - immunology
Natural killer cells
Proto-Oncogene Proteins c-bcl-2 - metabolism
Real-Time Polymerase Chain Reaction
Signal transduction
Signal Transduction - immunology
Spleen
STAT4 Transcription Factor - metabolism
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins - metabolism
T lymphocytes
Viral infections
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Natural killer (NK) cells function in the recognition and destruction of host cells infected with pathogens. Many regulatory mechanisms govern the potent responses of NK cells, both at the cellular and molecular level. Ablation of microRNA (miRNA) processing enzymes demonstrated that miRNAs play critical roles in NK cell differentiation and function; however, the role of individual miRNAs requires further investigation. Using mice containing a targeted deletion of microRNA-155 (miR-155), we observed defects in NK cell maintenance and maturation at steady state, as well as in homeostatic proliferation in lymphopenic mice. In addition, we discovered that miR-155 is up-regulated in activated NK cells during mouse cytomegalovirus (MCMV) infection in response to signals from the proinflammatory cytokines IL-12 and IL-18 and through signal transducer and activator of transcription 4 (STAT4) signaling. Although miR-155 was found to be dispensable for cytotoxicity and cytokine production when triggered through activating receptors, NK cells lacking miR-155 exhibited severely impaired effector and memory cell numbers in both lymphoid and nonlymphoid tissues after MCMV infection. We demonstrate that miR-155 differentially targets Noxa and suppressor of cytokine signaling 1 (SOCS1) in NK cells at distinct stages of homeostasis and activation. NK cells constitutively expressing Noxa and SOCS1 exhibit profound defects in expansion during the response to MCMV infection, suggesting that their regulation by miR-155 promotes antiviral immunity.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1304410110