Title |
The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development
|
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Published in |
Frontiers in immunology, May 2017
|
DOI | 10.3389/fimmu.2017.00535 |
Pubmed ID | |
Authors |
Mirte Post, Angelica Cuapio, Markus Osl, Dorit Lehmann, Ulrike Resch, David M. Davies, Martin Bilban, Bernhard Schlechta, Wolfgang Eppel, Amit Nathwani, Dagmar Stoiber, Jan Spanholtz, Emilio Casanova, Erhard Hofer |
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. |
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