Nfil3-independent lineage maintenance and antiviral response of natural killer cells Journal Article


Authors: Firth, M. A.; Madera, S.; Beaulieu, A. M.; Gasteiger, G.; Castillo, E. F.; Schluns, K. S.; Kubo, M.; Rothman, P. B.; Vivier, E.; Sun, J. C.
Article Title: Nfil3-independent lineage maintenance and antiviral response of natural killer cells
Abstract: Development of the nsssatural killer (NK) cell lineage is dependent on the transcription factor Nfil3 (or E4BP4), which is thought to act downstream of IL-15 signaling. Nfil3-deficient mice lack NK cells, whereas other lymphocyte lineages (B, T, and NKT cells) remain largely intact. We report the appearance of Ly49H-expressing NK cells in Nfil3-/- mice infected with mouse cytomegalovirus (MCMV) or recombinant viruses expressing the viral m157 glycoprotein. Nfil3-/- NK cells at the peak of antigen-driven expansion were functionally similar to NK cells from infected wild-type mice with respect to IFN-γ production and cytotoxicity, and could comparably produce long-lived memory NK cells that persisted in lymphoid and nonlymphoid tissues for >60 d. We demonstrate that generation and maintenance of NK cell memory is an Nfil3-independent but IL-15-dependent process. Furthermore, specific ablation of Nfil3 in either immature NK cells in the bone marrow or mature peripheral NK cells had no observable effect on NK cell lineage maintenance or homeostasis. Thus, expression of Nfil3 is crucial only early in the development of NK cells, and signals through activating receptors and proinflammatory cytokines during viral infection can bypass the requirement for Nfil3, promoting the proliferation and long-term survival of virus-specific NK cells. © 2013 Firth et al.
Journal Title: Journal of Experimental Medicine
Volume: 210
Issue: 13
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2013-12-16
Start Page: 2981
End Page: 2990
Language: English
DOI: 10.1084/jem.20130417
PROVIDER: scopus
PMCID: PMC3865482
PUBMED: 24277151
DOI/URL:
Notes: Export Date: 3 February 2014 -- CODEN: JEMEA -- Source: Scopus
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MSK Authors
  1. Joseph C Sun
    135 Sun
  2. Matthew Firth
    7 Firth
  3. Sharline Madera
    11 Madera