Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
Xiaoping Zhang
Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice - Mwanza: BioMed Central & Tanzania Catholic University of Health and Allied Sciences [CUHAS – Bugando] 25 June 2018 - Pages 1-11 - BMC immunology Volume 19 Issue 1 .
Abstract
Background: Potassium channel tetramerisation domain containing 9 (KCTD9), a member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be increased particularly in NK cells of patients with HBV-induced acute-on-chronic liver failure (HBV-ACLF) and experimental viral fulminant hepatitis. Knockdown of KCTD9 in immortalized NK cells inhibits cytokines production and cytotoxicity. As NK cell activation was shown to exacerbate liver damage in viral fulminant hepatitis, we propose that target inhibition of KCTD9 may prohibit NK cells activity and thus ameliorate liver damage in viral fulminant hepatitis.
Result: Hydrodynamic delivery of plasmid expressing short-hairpin RNA against KCTD9 resulted in impaired NK cells function as demonstrated by reduced cytokine production and cytotoxicity, and ameliorated liver injury as manifested by improved liver histology and survival rate. In contrast, delivery of plasmid expressing KCTD9 led to deteriorated disease progression.
Conclusion: Interference with KCTD9 expression exert beneficial effect in viral fulminant hepatitis therapy. Such effect may be mediated by impairment of NK cell activation.
1471-2172 = KCTD9 Short hairpin RNA NK cell Liver failure MHV-3
Phone: +255 28 298 3384 Fax: +255 28 298 3386 Email: vc@bugando.ac.tz Website: www.bugando.ac.tz
Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice - Mwanza: BioMed Central & Tanzania Catholic University of Health and Allied Sciences [CUHAS – Bugando] 25 June 2018 - Pages 1-11 - BMC immunology Volume 19 Issue 1 .
Abstract
Background: Potassium channel tetramerisation domain containing 9 (KCTD9), a member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be increased particularly in NK cells of patients with HBV-induced acute-on-chronic liver failure (HBV-ACLF) and experimental viral fulminant hepatitis. Knockdown of KCTD9 in immortalized NK cells inhibits cytokines production and cytotoxicity. As NK cell activation was shown to exacerbate liver damage in viral fulminant hepatitis, we propose that target inhibition of KCTD9 may prohibit NK cells activity and thus ameliorate liver damage in viral fulminant hepatitis.
Result: Hydrodynamic delivery of plasmid expressing short-hairpin RNA against KCTD9 resulted in impaired NK cells function as demonstrated by reduced cytokine production and cytotoxicity, and ameliorated liver injury as manifested by improved liver histology and survival rate. In contrast, delivery of plasmid expressing KCTD9 led to deteriorated disease progression.
Conclusion: Interference with KCTD9 expression exert beneficial effect in viral fulminant hepatitis therapy. Such effect may be mediated by impairment of NK cell activation.
1471-2172 = KCTD9 Short hairpin RNA NK cell Liver failure MHV-3
Phone: +255 28 298 3384 Fax: +255 28 298 3386 Email: vc@bugando.ac.tz Website: www.bugando.ac.tz