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Front Immunol. 2017 May 15;8:535. doi: 10.3389/fimmu.2017.00535. eCollection 2017.

The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development.

Author information

1
Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
2
Department of Oncology, University College London Cancer Institute, London, UK.
3
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
4
Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
5
Ludwig Boltzmann Institute of Cancer Research, Vienna, Austria.
6
Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
7
Glycostem Therapeutics, Oss, Netherlands.
8
Institute of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Abstract

We identified ZNF683/HOBIT as the most highly upregulated transcription factor gene during ex vivo differentiation of human CD34+ cord blood progenitor cells to CD56+ natural killer (NK) cells. ZNF683/HOBIT mRNA was preferentially expressed in NK cells compared to other human peripheral blood lymphocytes and monocytes. During ex vivo differentiation, ZNF683/HOBIT mRNA started to increase shortly after addition of IL-15 and further accumulated in parallel to the generation of CD56+ NK cells. shRNA-mediated knockdown of ZNF683/HOBIT resulted in a substantial reduction of CD56-CD14- NK-cell progenitors and the following generation of CD56+ NK cells was largely abrogated. The few CD56+ NK cells, which escaped the developmental inhibition in the ZNF683/HOBIT knockdown cultures, displayed normal levels of NKG2A and KIR receptors. Functional analyses of these cells showed no differences in degranulation capacity from control cultures. However, the proportion of IFN-γ-producing cells appeared to be increased upon ZNF683/HOBIT knockdown. These results indicate a key role of ZNF683/HOBIT for the differentiation of the human NK-cell lineage and further suggest a potential negative control on IFN-γ production in more mature human NK cells.

KEYWORDS:

CD56; NK-cell development; ZNF683/HOBIT; ex vivo differentiation; natural killer cells

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