Post, M;
Cuapio, A;
Osl, M;
Lehmann, D;
Resch, U;
Davies, DM;
Bilban, M;
... Hofer, E; + view all
(2017)
The Transcription Factor ZnF683/hOBiT regulates human NK-cell Development.
Frontiers in Immunology
, 8
, Article 535. 10.3389/fimmu.2017.00535.
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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.
| Type: | Article |
|---|---|
| Title: | The Transcription Factor ZnF683/hOBiT regulates human NK-cell Development |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2017.00535 |
| Publisher version: | http://doi.org/10.3389/fimmu.2017.00535 |
| Language: | English |
| Additional information: | Copyright © 2017 Post, Cuapio, Osl, Lehmann, Resch, Davies, Bilban, Schlechta, Eppel, Nathwani, Stoiber, Spanholtz, Casanova and Hofer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | ZNF683/HOBIT, natural killer cells, CD56, ex vivo differentiation, NK-cell development |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050897 |
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