Lack of DOCK8 impairs the primary biologic functions of human NK cells and abrogates CCR7 surface expression in a WASP-independent manner.
Clin Immunol
; 237: 108974, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35278713
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Fatores de Troca do Nucleotídeo Guanina
/
Citocinese
/
Receptores CCR7
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article