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

   

Authors:	Zawislak, C. L.; Beaulieu, A. M.; Loeb, G. B.; Karo, J.; Canner, D.; Bezman, N. A.; Lanier, L. L.; Rudensky, A. Y.; Sun, J. C.
Article Title:	Stage-specific regulation of natural killer cell homeostasis and response against viral infection by microRNA-155
Abstract:	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 cyto-megalovirus (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.
Keywords:	signal transduction; controlled study; protein expression; gene deletion; nonhuman; lymphocyte proliferation; animal cell; mouse; animals; mice; mus; cell maturation; steady state; animal experiment; animal model; immunoregulation; lymphocytopenia; gene expression regulation; chromatin immunoprecipitation; natural killer cell; adoptive transfer; killer cells, natural; effector cell; upregulation; virus infection; micrornas; memory cell; homeostasis; luciferases; proto-oncogene proteins c-bcl-2; cytomegalovirus infection; interleukin 12; lymphocyte count; virus immunity; interleukin 18; herpesviridae infections; interleukin-12; interleukin-18; suppressor of cytokine signaling proteins; protein noxa; stat4 protein; stat4 transcription factor; real-time polymerase chain reaction; microrna 155; suppressor of cytokine signaling 1; muromegalovirus; maize chlorotic mottle virus
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	110
Issue:	17
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2013-04-23
Start Page:	6967
End Page:	6972
Language:	English
DOI:	10.1073/pnas.1304410110
PROVIDER:	scopus
PMCID:	PMC3637707
PUBMED:	23572582
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84876868417&partnerID=40&md5=cb19161ffe88965e049acbac0ec5c28c
Notes:	--- - "Export Date: 3 June 2013" - "CODEN: PNASA" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/41354