The Transcription Factor Promyelocytic Leukemia Zinc Finger Protein Is Associated With Expression of Liver‐Homing Receptors on Human Blood CD56bright Natural Killer Cells

Abstract

The transcription factor promyelocytic leukemia zinc finger protein (PLZF) is involved in the development of natural killer (NK) cells and innate lymphoid cells, including liver‐resident NK cells in mice. In human NK cells, the role of PLZF in liver residency is still unknown. Expression of PLZF in matched human peripheral blood‐ and liver‐derived NK cells and the association of PLZF expression with surface molecules and transcription factors relevant for tissue residency were investigated using multiparameter flow cytometry and assessing single‐cell messenger RNA (mRNA) levels. Intrahepatic cluster of differentiation (CD)56bright NK cells expressed significantly higher levels of PLZF than peripheral blood CD56bright NK cells, which were predominantly PLZFlo. Expression of PLZF was highest within C‐X‐C motif chemokine receptor 6 (CXCR6)+CD69+ liver‐resident NK cells among intrahepatic CD56bright NK cell populations. Association of PLZF with liver‐residency markers was also reflected at mRNA levels. A small PLZFhiCD56bright NK cell population was identified in peripheral blood that also expressed the liver‐residency markers CXCR6 and CD69 and shared functional characteristics with liver‐resident NK cells. Conclusion: PLZF is implicated as part of a transcriptional network that promotes liver residency of human NK cells. Expression of liver‐homing markers on peripheral blood PLZFhiCD56bright NK cells identifies an intermediate population potentially contributing to the maintenance of liver‐resident NK cells.

Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level

“…The data processing was performed as described previously ( Hess et al., 2020 ). In short, cells lacking detectable mRNA in two out of the three reference genes ( B2M, RPL13A, GAPDH ) were excluded from further analysis.…”

Transcriptional Regulation of Natural Killer Cell Development and Functions

“…Promyelocytic leukemia zinc finger (PLZF, encoded by Zbtb16 gene) is a member of the BTB-zinc finger TF family, and is present in both human and mouse NK cells [266,267]. Human adaptive NK cells display significantly downregulated expression of PLZF, which suggests that lack of PLZF marks a gain of human adaptive NK cells [268].…”

“…Human adaptive NK cells display significantly downregulated expression of PLZF, which suggests that lack of PLZF marks a gain of human adaptive NK cells [268]. In addition, PLZF is highly associated with markers of liver-resident NK cells in humans [266]. Zbtb32 is another TF from the BTB-zinc finger TF family.…”

The Correlations Between the Expression of SSTR2, SSTR5 Proteins and Clinicopathological Parameters as well as Prognosis of Gastric Neuroendocrine Neoplasms

“…Meanwhile, CD-56 was an independent factor affecting the prognosis of G-NENs patients in the SSTR2 positive group, SSTR2 negative group and SSTR5 positive group, which suggests that SSTR2 and SSTR5 are closely related to the expression of CD-56. Although CD-56 in patients with G-NENs is rarely studied, the expression of CD-56 in acute myeloid leukemia is more studied, which belongs to the member of the super-immune protein family and has a cellular regulatory effect, indicating poor prognosis of AML [19,20]. These also indirectly re ected the positive association between SSTR2, SSTR5 expression and tumor prognosis.…”