Enhanced Calcium Signal Induces NK Cell Degranulation but Inhibits Its Cytotoxic Activity.
J Immunol
; 208(2): 347-357, 2022 01 15.
Article
en En
| MEDLINE
| ID: mdl-34911773
ABSTRACT
Although the mechanism of NK cell activation is still unclear, the strict calcium dependence remains the hallmark for lytic granule secretion. A plethora of studies claiming that impaired Ca2+ signaling leads to severely defective cytotoxic granule exocytosis accompanied by weak target cell lysis has been published. However, there has been little discussion about the effect of induced calcium signal on NK cell cytotoxicity. In our study, we observed that small-molecule inhibitor UNC1999, which suppresses global H3K27 trimethylation (H3K27me3) of human NK cells, induced a PKD2-dependent calcium signal. Enhanced calcium entry led to unbalanced vesicle release, which resulted into fewer target cells acquiring lytic granules and subsequently being killed. Further analyses revealed that the ability of conjugate formation, lytic synapse formation, and granule polarization were normal in NK cells treated with UNC1999. Cumulatively, these data indicated that induced calcium signal exclusively enhances unbalanced degranulation that further inhibits their cytotoxic activity in human NK cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Degranulación de la Célula
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Señalización del Calcio
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Canales Catiónicos TRPP
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Proteína Potenciadora del Homólogo Zeste 2
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2022
Tipo del documento:
Article