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

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

doi:10.3389/fimmu.2017.00535

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

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

Research output: Journal article (peer-reviewed) › Journal article

30 Citations (Scopus)

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.

Original language	English
Article number	535
Pages (from-to)	535
Journal	Frontiers in Immunology
Volume	8
Issue number	MAY
DOIs	https://doi.org/10.3389/fimmu.2017.00535
Publication status	Published - May 2017
Externally published	Yes

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title = "The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development",

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.",

author = "Mirte Post and Angelica Cuapio and Markus Osl and Dorit Lehmann and Ulrike Resch and Davies, {David M} and Martin Bilban and Bernhard Schlechta and Wolfgang Eppel and Amit Nathwani and Dagmar Stoiber and Jan Spanholtz and Emilio Casanova and Erhard Hofer",

note = "Publisher Copyright: {\textcopyright} 2017 Post, Cuapio, Osl, Lehmann, Resch, Davies, Bilban, Schlechta, Eppel, Nathwani, Stoiber, Spanholtz, Casanova and Hofer.",

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T1 - The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development

AU - Post, Mirte

AU - Cuapio, Angelica

AU - Osl, Markus

AU - Lehmann, Dorit

AU - Resch, Ulrike

AU - Davies, David M

AU - Bilban, Martin

AU - Schlechta, Bernhard

AU - Eppel, Wolfgang

AU - Nathwani, Amit

AU - Stoiber, Dagmar

AU - Spanholtz, Jan

AU - Casanova, Emilio

AU - Hofer, Erhard

PY - 2017/5

Y1 - 2017/5

N2 - 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.

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

Abstract

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