miR-155 regulates IFN-γ production in natural killer cells
Open Access
- 12 April 2012
- journal article
- Published by American Society of Hematology in Blood
- Vol. 119 (15), 3478-3485
- https://doi.org/10.1182/blood-2011-12-398099
Abstract
MicroRNAs (miRs) are small, noncoding RNA molecules with important regulatory functions whose role in regulating natural killer (NK) cell biology is not well defined. Here, we show that miR-155 is synergistically induced in primary human NK cells after costimulation with IL-12 and IL-18, or with IL-12 and CD16 clustering. Over-expression of miR-155 enhanced induction of IFN-γ by IL-12 and IL-18 or CD16 stimulation, whereas knockdown of miR-155 or its disruption suppressed IFN-γ induction in monokine and/or CD16-stimulated NK cells. These effects on the regulation of NK cell IFN-γ expression were found to be mediated at least in part via miR-155's direct effects on the inositol phosphatase SHIP1. Consistent with this, we observed that modulation of miR-155 overrides IL-12 and IL-18–mediated regulation of SHIP1 expression in NK cells. Collectively, our data indicate that miR-155 expression is regulated by stimuli that strongly induce IFN-γ in NK cells such as IL-12, IL-18, and CD16 activation, and that miR-155 functions as a positive regulator of IFN-γ production in human NK cells, at least in part via down-regulating SHIP1. These findings may have clinical relevance for targeting miR-155 in neoplastic disease.Keywords
This publication has 48 references indexed in Scilit:
- miR-150 regulates the development of NK and iNKT cellsThe Journal of Experimental Medicine, 2011
- MicroRNAs in NF- B signalingJournal of Molecular Cell Biology, 2011
- Innate or Adaptive Immunity? The Example of Natural Killer CellsScience, 2011
- Next-generation sequencing identifies the natural killer cell microRNA transcriptomeGenome Research, 2010
- Inositol phosphatase SHIP1 is a primary target of miR-155Proceedings of the National Academy of Sciences of the United States of America, 2009
- Colocalization of the IL-12 receptor and FcγRIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-γBlood, 2008
- B-cell Receptor Activation Induces BIC/miR-155 Expression through a Conserved AP-1 ElementPublished by Elsevier BV ,2008
- The PP2A inhibitor SET regulates natural killer cell IFN-γ productionThe Journal of Experimental Medicine, 2007
- Requirement of bic/microRNA-155 for Normal Immune FunctionScience, 2007
- Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic miceProceedings of the National Academy of Sciences of the United States of America, 2006