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.

Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity

“…In contrast, NK cells provide a delayed source of IFN-γ, since they migrate from the circulation into the tissues only at a later time. However, since Hobit has been recently implicated in human NK cell development (Post et al, 2017), it will be important to confirm that deficiency of Hobit results in a selective and complete impairment of ILC1s in the liver and in other tissues in general.…”

Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells

“…S5C). However, both clusters also displayed expression of genes associated with NK cell function, including FCGR3A/B (CD16, employed by NK cells for antibodydependent cellular cytotoxicity), and ZNF683 (HOBIT, a transcription factor highly expressed by human NK cells(48) and used as a surrogate for equine NK cells by RT-PCR (49)(Fig. 5E);…”

Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics

“…Blimp-1 controls the generation of these CD8 + T rm cells in the lungs [219] . However, in mature human NK cells, ZNF683 or Hobit negatively regulates IFN-γ production by mature human NK cells [220] . Therefore, the ZNF683 expression in human NK cells isolated from COVID-19 should also be explored as severe COVID-19 patients fail to produce IFN-γ.…”