Lack of DOCK8 impairs the primary biologic functions of human NK cells and abrogates CCR7 surface expression in a WASP-independent manner

Lack of DOCK8 impairs the primary biologic functions of human NK cells and abrogates CCR7 surface expression in a WASP-independent manner

Copyright © 2022 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 237(2022) vom: 04. Apr., Seite 108974
1. Verfasser: Patrizi, Ornella (VerfasserIn)
Weitere Verfasser: Baronio, Manuela, Gazzurelli, Luisa, Rossi, Stefano, Rezzola, Sara, Marcenaro, Emanuela, Plebani, Alessandro, Badolato, Raffaele, Parolini, Silvia, Lougaris, Vassilios, Tabellini, Giovanna
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article C-C motif chemokine receptor 7 Dedicator of cytokinesis 8 Natural killer cells Wiskott-Aldrich syndrome protein CCR7 protein, human CD56 Antigen DOCK8 protein, human Guanine Nucleotide Exchange Factors Receptors, CCR7 mehr... WAS protein, human Wiskott-Aldrich Syndrome Protein
Beschreibung
Zusammenfassung:Copyright © 2022 Elsevier Inc. All rights reserved.
Dedicator of Cytokinesis 8 (DOCK8) deficiency is a rare form of autosomal recessive combined immunodeficiency. The effect of DOCK8 deficiency on Natural Killer cell biology has not been fully elucidated yet. Thus, we undertook a detailed phenotypic and functional evaluation of NK cells from seven patients with DOCK8 deficiency. Patients' immature CD56bright NK cells were defective in IFN-γ secretion, while their mature CD56dim NK cells showed impaired cytotoxicity, partially rescued upon rIL-2 addition. Cross-linking of NK cell receptors revealed a specific defect in the CD3 zeta chain-dependent activation pathway in DOCK8 deficiency. Lack of DOCK8, but not of WASP, impaired CCR7 expression on human CD56bright NK cells, a critical receptor for their migration to secondary lymph nodes. Evaluation of a patient's lymph node showed a severe reduction in NK cells that showed increased intracellular expression of CCR7. Our data suggest that DOCK8 deficiency variably affects NK cell homeostasis in humans
Beschreibung:Date Completed 18.04.2022
Date Revised 31.05.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2022.108974