DOCK8 Drives Src-Dependent NK Cell Effector Function
Conor J Kearney, Stephin J Vervoort, Kelly M Ramsbottom, Andrew J Freeman, Jessica Michie, Jane Peake, Jean-Laurent Casanova, Capucine Picard, Stuart G Tangye, Cindy S Ma, Ricky W Johnstone, Katrina L Randall, Jane Oliaro
JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2017
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause an autosomal recessive form of hyper-IgE syndrome, characterized by chronic immunodeficiency with persistent microbial infection and increased incidence of malignancy. These manifestations suggest a defect in cytotoxic lymphocyte function and immune surveillance. However, how DOCK8 regulates NK cell-driven immune responses remains unclear. In this article, we demonstrate that DOCK8 regulates NK cell cytotoxicity and cytokine production in response to target cell engagement or receptor ligation. Genetic ablation of DOCK8 in human NK cells attenuated cytokine transcription and secretion through inhibition of Src family kinase activ..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was supported by the National Health and Medical Research Council of Australia (Grant 1079318).