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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.

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


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.


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

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