Cytokine secretion and NK cell activity in human ADAM17 deficiency
| Autor: | Ofer Mandelboim, Eli M. Eisenstein, Pinchas Tsukerman, Yotam Bar-On, Eitan Wong, Irit Sagi, Marion Werner, Einat Seidel, Maor Chavkin, Polina Stepensky, Dominik Schmiedel, Orly Elpeleg, Vered Molho-Pessach, Diana Averbuch, Barak Yaacov, Rachel Yamin, Noa S. Kaynan |
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| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Male Stimulation chemical and pharmacologic phenomena NK cells CD16 ADAM17 Protein GPI-Linked Proteins Lymphocyte Activation Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine Immune system Fatal Outcome Cell Line Tumor Medicine Humans Genetic Predisposition to Disease Immune response Receptor 030304 developmental biology Antibody-dependent cell-mediated cytotoxicity 0303 health sciences biology business.industry Receptors IgG ADAM17 deficiency Antibody-Dependent Cell Cytotoxicity Immunologic Deficiency Syndromes Research Paper: Immunology Immunity Immunity Innate 3. Good health Killer Cells Natural ADAM Proteins Phenotype Oncology 030220 oncology & carcinogenesis Child Preschool Immunology biology.protein Leukocytes Mononuclear Cytokines Immunology and Microbiology Section Cytokine secretion Antibody business ADCC |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Genetic deficiencies provide insights into gene function in humans. Here we describe a patient with a very rare genetic deficiency of ADAM17. We show that the patient's PBMCs had impaired cytokine secretion in response to LPS stimulation, correlating with the clinical picture of severe bacteremia from which the patient suffered. ADAM17 was shown to cleave CD16, a major NK killer receptor. Functional analysis of patient's NK cells demonstrated that his NK cells express normal levels of activating receptors and maintain high surface levels of CD16 following mAb stimulation. Activation of individual NK cell receptors showed that the patient's NK cells are more potent when activated directly by CD16, albeit no difference was observed in Antibody Depedent Cytotoxicity (ADCC) assays. Our data suggest that ADAM17 inhibitors currently considered for clinical use to boost CD16 activity should be cautiously applied, as they might have severe side effects resulting from impaired cytokine secretion. |
| Databáze: | OpenAIRE |
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