1. The Transcription Factor Promyelocytic Leukemia Zinc Finger Protein Is Associated With Expression of Liver‐Homing Receptors on Human Blood CD56bright Natural Killer Cells
- Author
-
Hanna Goebels, Lutz Fischer, Christoph Schramm, Martina Koch, Gisa Tiegs, Wilhelm Salzberger, Karl J. Oldhafer, Tobias Poch, Annika E. Langeneckert, Adrian F. Sagebiel, Annerose E. Ziegler, Marcus Altfeld, Laura Richert, Gloria Martrus, Leonard U. Hess, Gevitha Ravichandran, Sven Hendrik Hagen, Madeleine J. Bunders, Sebastian Lunemann, Heinrich Pette Institute [Hamburg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Semmelweis University of Medicine [Budapest], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Supported by the German Research Foundation (SFB841 to M.A., C.S., G.T., and S.L., SFB841 graduate school to A.Z., H.G., and L.H., and KFO306 to M.A., C.S., A.L., T.P., G.R., and G.T.) and the Helmut and Hannelore Greve Foundation (to C.S.)., Johannes Gutenberg - Universität Mainz (JGU), and Richert, Laura
- Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology ,Population ,Cell ,C-C chemokine receptor type 6 ,Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,lcsh:RC799-869 ,Receptor ,education ,Transcription factor ,030304 developmental biology ,0303 health sciences ,Messenger RNA ,education.field_of_study ,Hepatology ,Cluster of differentiation ,Innate lymphoid cell ,Original Articles ,SISTM ,3. Good health ,medicine.anatomical_structure ,Cancer research ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Original Article ,lcsh:Diseases of the digestive system. Gastroenterology ,030215 immunology - 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., High expression of PLZF was associated with co‐expression of the liver‐residency markers CXCR6 and CD69 on human CD56bright NK cells not only in livers but also in a small NK cell subset in peripheral blood. These CXCR6+CD69+PLZFhi CD56bright NK cells in peripheral blood furthermore displayed functional characteristics similar to liver‐resident NK cells, suggesting that these cells might represent an intermediate stage and potentially contribute to the maintenance of liver‐resident NK cells.
- Published
- 2020