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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development.
Duncan M Gascoyne1, Elaine Long, Henrique Veiga-Fernandes
1Molecular Haematology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
Nature Immunology
|September 15, 2009
Summary
The transcription factor E4BP4 (also known as NFIL3) is essential for the development of natural killer (NK) cells. Mice lacking E4BP4 specifically lack NK cells, highlighting its critical role in innate immunity.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Natural killer (NK) cells are vital lymphocytes in innate immunity.
- The lineage commitment of NK cells remains poorly understood compared to T and B cells.
Purpose of the Study:
- To investigate the role of the transcription factor E4BP4 (NFIL3) in NK cell lineage commitment and development.
- To elucidate the molecular mechanisms underlying NK cell generation.
Main Methods:
- Utilized E4BP4-deficient mice (Nfil3(-/-)) to study NK cell development.
- Analyzed hematopoietic progenitor cells and NK cell-mediated cytotoxicity.
- Investigated the role of E4BP4 downstream of the interleukin 15 receptor (IL-15R) and its interaction with Id2.
Main Results:
- E4BP4-deficient mice completely lacked NK cells but retained B, T, and NKT cells.
- NK cell-mediated cytotoxicity was severely impaired in E4BP4-deficient mice.
- Overexpression of E4BP4 promoted NK cell production from hematopoietic progenitor cells.
Conclusions:
- E4BP4 is a critical and essential transcription factor for the generation of the NK cell lineage.
- E4BP4 acts in a cell-intrinsic manner, downstream of IL-15R signaling and via Id2.
- E4BP4-deficient mice serve as a valuable model for studying NK cell functions in immunity and disease.
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